2nd Test Material Flashcards

1
Q

What is homeostasis the framework for?

A

for the studying and understanding of physiology

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2
Q

Who is Claude Bernard?

A
  • Father of modern physiology
  • Our internal environment remains remarkably constant despite changes in the external milieu provides stable conditions for cells in body
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3
Q

Walter Cannon?

A

Coined the term “homeostasis” to describe the relative stability of the internal environment

Homeo= “unchanging”
Stasis= “Static”

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4
Q

What does homestatsis regulate by?

A

Negative feedback loop: system where output of a process acts to counteract or reduce initial stimulus, maintain stability

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5
Q

What are the parts of homeostatic control?

A

Sensor: contstantly monitors

Integrating centre: coordinates

Response system: changes

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6
Q

How does the response system act… right before it goes back to sensor?

A

Negative feedback

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7
Q

What are the major regulatory systems?

A
  • Skin
  • Cardiovascular
  • Renal
  • Digestive
  • Respiratory
  • Musculo-skeletal
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8
Q

What are the regulated factors of the major regulatory systems?

A
  • Water
  • Electrolytes/pH
  • Nitrogenous compounds
  • Oxygen
  • CO2
  • Temperature
  • Toxicants
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9
Q

Where is homeostasis maintained largely part of?

A

Endocrine system

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10
Q

What may result from loss of homeostasis?

A

Disease, if hormone mediators (signals) are disrupted the endocrine system may also become dsyregulated

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11
Q

Diabetes mellitus is the…

A

6th leading cause of death in Canada

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12
Q

How many are affected by thyroid disorders?

A

Around 5% of total population increasing with age

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13
Q

How many are affected by endocrine ovarian disorders?

A

6% of female population are the most common cause of infertility

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14
Q

What does hyper-function, hypo-function, resistance mean?

A

Too much hormone, too little hormone, too little effect there but doesnt get expressed

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15
Q

What is the study of the endocrine system?

A
  • The study of hormones and the actions of hormones
  • The study of how endocrine glands regulate the physiology and behaviour of animals
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16
Q

Where does the term hormone come from?

A

To excite or arouse

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17
Q

What is the endocrine gland defined as?

A

A tissue which releases (secretes) a substance into the blood steam; this substance then travels via the blood to influence a target cell

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18
Q

What did the classic minkowski experiment find?

A

Discovery of insulin
- If you surgically remove pancreas in dog; dog develops symptoms of diabetes
- If you implant pieces of pancrease under skin; prevents symptoms of diabetes

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19
Q

What did Banting and Best Discover?

A

Discovery of insulin; identified antidiabetic substance in pancreatic extracts
- Injecting extracts prevents symptoms of diabetes ie; prevents elevated blood glucose

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20
Q

What is insulin?

A
  • Peptide hormone produced by beta cells of the pancreas
  • Promotes absorption of glucose from blood to skeletal muscle and fat tissue
  • Inactive, stored form= hexamer, zinc ion & histidine residues
  • Active form= monomer
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21
Q

What makes a chemical a hormone?

A
  1. Most proteins & polypeptides (<100 amino acids)
  2. Steroids (cholesterol derivatives)
  3. Glycoproteins
  4. Amines (catecholamines or thyroid)
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22
Q

What does autocrine do?

A

Target sites on same cell

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23
Q

What does paracrine do?

A

Secretory cell to adjacent target cell

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24
Q

What does endocrine do?

A

Hormone secretion into blood by endocrine gland

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25
What do hormones bind to?
Specific receptors on target cells
26
Each hormone has high...
Specifity; but some can bind to non-specific receptors
27
The receptor-hormone complex is continuously...
Replaced to maintain signalling
28
Most hormone receptors are located in the...
Plasma membrane of target cells
29
What type of transport is in peptide and amine (cat)
Dissolved in plasma; attached to membrane
30
What type of transport is in steroid and amine (thyroid)
in cell; bound to carrier proteins
31
Where does hormone bind to?
Extracellular domain of the receptor and activates one or more cytoplasmic signalling pathway
32
Many of these pathways involve...
phosporylation and enzyme activation
33
Some of the pathways lead to the DNA/mRNA/protein pathway response; others have local effect in target cell
Yes!
34
Examples of peptide (insulin); amine (cat) (epinephrine); dissolved in plasma
Adenylate cyclase pathway: 1. Hormone+receptor, G-proteins dissociate 2. alpha subunit activates AC 3. Catalyzes product of cAMP (ATP to cAMP) 4. Removes regulatory unit from PK (PKA) 5. PK activates other molecules (hormonal response) Epinephrine & adenylate cyclase: 1. Epinephrine binds to beta- adrenergic receptor on liver cell 2. G-proteins activated- subunit carrying GDP dissociates, GDP to GTP 3. Subunit activates adenylyl cyclase which catalyzes ATP into cAMP 4. cAMP activtes PKA, which activates phosphorylase 5. Phosphorylase converts glycogen to glucose-6-phosphate 6. Glucose-6-phosphate into glucose (released from liver)
35
What did Robert Lefkowitz and Brian Kobilka do?
- Recieved the 2012 Nobel prize in chemistry - How the billions of cells in our body sense their environments - Focus on G protein-coupled receptors (proteins that reach through cell walls) - Understanding how these proteins work has been crucial to unravelling the complex network of signalling between cells
36
What are examples of processes that are bound to carrier proteins example steroid and amine (thyroid)?
Phospholipase C-Ca2+ pathways: 1. Hormone + receptor, G-proteins dissociate 2. Activates PLC (photolipase C) 3. Causes breakdown of membrane phospholipid to IP3 4. IP3 binds to endoplasmic reticulum 5. Release of stored Ca2+ into cytoplasm 6. Ca2+ activates other molecules (hormonal response) Steroid hormone receptors: 1. Steroid hormone (eg estrogen, androgen) transported bound to plasma carrier protein - Lipophillic (ie they move across plasma membrane) 2. Steroid hormone binds cell cytoplasm receptor 3. Translocates to the nucleus, binds to DNA - acts as transcription factor 4. Stimulates gene transcription 5. Protein products 6. Response basically steroid hormones travel in blood bound to carrier proteins, being lipophilic, they pass through cell membrane, in the cell, they bind to cytoplasmic receptors, the receptor-hormone complex moves into nucleus and binds DNA, activates gene transcription, leading to protein production, initiates cellular response Thyroid receptors: 1. Thyroxine (T4)+carrier binding protein 2. T4 into T3 (triiodothyronine) 3. T3 uses binding proteins to enter nucleus 4. Hormone receptor complex binds DNA 5. New mRNA 6. Protein 7. Response
37
What does alpha-adrenergic receptors activate?
phospholipase C (via Gq) (PLC)
38
What do beta-adrenergic receptors activate?
Adenylate cyclase (via Gs)
39
G-alpha subunits fall into several sub-types...
G(s) alpha, G(a) alpha etc
40
What is the general mechanism of action for the hormones of the hypothalamic-anterior pituitary-peripheral target axes...
Hypothalmic neuroendocrine cells (hormone 1; blood vessels) Anterior pituitary cells (hormone 2; general circulation) Splits into target tissues (endocrine and non-endocrine) (goes into general circulation) Ellicits a tissue response Summary: goes from hypothalamus to anteriior pituitary, release hormone to peripheral targets to ellicit effects
41
Where is the pituitary gland connected?
connected to hypothalamus through infundibulum (stalk)
42
What is the pituitary gland protected by?
Bone
43
What is the anterior pituitary/ adenohypophysis?
Endocrine gland (one above and on left)
44
What is the posterior pituitary/neurohypophysis?
Extension of neural tissue
45
What does pars distalis do?
Makes up lobe of anterior pituitary
46
What does pars tuberlis do?
Tissue that wraps around infundibulum
47
What does pars intermedia do?
group of tissues between the anterior and posterior lobe (only exists in fetus) in fetus all 3, in adults only two the distalis and the tuberalis
48
What are the pars tuberlalis, the pars intermedia and the pars distalis from?
Anterior pituitary
49
What is the posterior pituitary made up of?
Pars nervosa and infundibular stalk
50
What does pars nervosa do?
Contact with infidibulum or stalk
51
Posterior is connected to nerves from hypothalamus true or false
True
52
What is anterior pituitary connected to from hypothalamus?
Connected only to blood vessels
53
What are some hormones being released by the neurosecretory to stimulate pituitary (anterior)
- Dopamine - Prolactin releasing hormone (PRH) -Thyrotropin-releasing hormone (TRH) -Corticotropin-releasing hormone (CRH) -Somatostatin (GHIH) - Growth hormones releasing hormone (GHRH) - Gonadotrophin-releasing hormone (GnRH)
54
What does dopamine (PIH) do?
Inhibits secretion of prolactin, also called that since prolactin inhibiting hormone
55
What does prolactin releasing hormone do?
Stimulates release of prolactin
56
What does thyrotropin-releasing hormone do?
Regulates secretion of thyroid stimulating hormone (TSH)
57
What does cortico-releasing hormone do?
Regulates secretion of adrencoticotrophic hormone (ACTH)
58
What does somatostatin do (GHIH)?
Inhibits secretion of growth hormone (GH), also called this since growth hormone inhibiting hormone
59
What does growth hormone releasing hormone (GHRH) do?
Stimulates secretion of GH
60
What does gonadotrophin-releasing hormone (GnRH) do?
Regulates secretion of gonadotrophin-relasing hormones, lutenizing hormones (LH), and follicle stimulating hormones (FSH)
61
What does IH and RH mean?
IH means inhibiting hormone and RH is releasing hormone
62
Althought the anatomical orginziation changes slightly in the pituitary and hypothalmus, from species to species, can see that they are in tact and differ
true
63
What is the hypothalamic anterior pituitary adrenal cortex axis known as?
Stress axis
64
When body is stressed what happens?
1. When body is stressed, neurosecretory cells of hypothalamus are going to release CRH (corticoidtropin releasing hormone) 2. Stimulate anterior pituitary in network of blood vessels to stimulate anterior pituiatary to secrete ACTH or adrenocorticotrophic hormone 3. ACTH travels through circulation to the adrenal cortex of the adrenal glands which is on top of the kidney which stimulates cortex of adrenal gland to secrete increasing amount of glucocorticoids (cortisol) - proceeds with catabolism (break down of proteins, stimulate liver to make amino acids to glucose)
65
What does gluogensis result in? and its effect on being stressed for example being chased by a bear
Rise of blood glucose levels; causes stress which causes breakdown of fats and muscle which allows glucose in the blood for quick energy
66
What happens during exam season?
Body is very stressed during exams, lots of cortisol, supressing your immune system saving energy for stressful times
67
What does the hypothalamic anterior pituitary adrenal cortex have via feedback loop?
Negative, once reaction has subsided, cortisol is going to feed back to anterior pituitary as well as hypothalamus to stop CRH and ACTH
68
What does increase of CRH cause?
Increase in ACTH or otherwise known as POMC (proopiomelanocortin) which increases levels of ACTH, POMC is a pro hormone
69
What is CRH?
Corticotropin releasing hormone (from hypothalamus)
70
What is ACTH?
Adrenocorticotoropic hormone (from anterior pituitary)
71
What is cortisol?
Glucocorticoid, chronic stress hormone
72
is homeostasis in a negative feeback loop?
YES
73
Where is CRH coming from?
From parvocellular neuroendocrine cells within the nucleis of hypothalmus (hypothalamic paraventricular nucleus)
74
How is CRH release and inhibited?
Stimulation (activation): - Noradrenaline triggers CRH production - Stimulates pre-proCRH genes and protein (precursour) (196 AA) - Processed into CRH (41 AA) - Released in pulses Inhibition (suppression) - Cortisol (stress hormone) block CRH release and may reduce gene expression; may stop both CRH and proCRH expression
75
Where is CRH released from?
At median eminence (base of brain) from neurosecretory nerve terminals, into blood vessels in the hypothalamic-pituitary portal system
76
Where do blood vessels carry the CRH to?
Carry CRH peptides to anterior lobe of pituitary where they stimulate cortiocotropes to secrete adrenocorticotropic hormone (ACTH)
77
What does ACTH do?
Adrenocorticotropic hormone (regulates adrenal cortex function)
78
What does MSH do?
Melanocyte stimulation hormone (skin pigmentation in response to UV radiation)
79
What does end do?
beta endorphin (analgesic roles in central nervous system)
80
What does enk do?
enkephalin (analgesic roles in fetus)
81
What does MC3,4,5 do?
receptors in hypothermia, hypotension, feeding behaviour, appetite)
82
What do convertases do?
Cleave at certain areas to get different proteins to help in these processes (only ACTH for now)
83
do adrenal glands cap the top spaces of the kidney
YES
84
What is the adrenal gland made up of?
2 distinct tissues that merged during development (similar to pituitary) Have adrenal cortex: secretes steroids (corticosteroids) 3 types of corticosteroids 1. Glucocorticoids (eg cortisol): controlled by ACTH (glucose for energy stress) 2. Mineralocoritcoids (eg aldosterone): controlled by renin-angiotensin system (sodium and potassium balance) 3. Sex steroids (eg testosterone): controlled by ACTH Adrenal medulla: modified sympathetic ganlia, secretes catecholamine (eg epinephrine)
85
Do adrenal glands stand on top of the kidney?
Yes
86
What does the zona glomerulosa secrete?
Mineralocorticoids (cortex of adrenal)
87
What does zona fasciculata secrete?
Glucocoritcoids (cortex of adrenal)
88
What does zona reticularis secrete?
Androgens (cortex of adrenal)
89
What types of hormones are we getting in the medulla?
Epinephrine
90
What is the dominaint glucocorticoid in humans?
cortisol
91
What is the dominaint glucocorticoid in animals esp rats?
Corticosterone
92
Why is cortisol important for life?
1. Promotes against hypoglycaemia (low blood sugar) 2. Promotes gluconeogenesis (increase blood sugar) 3. Plays a role in immune system - supresses immune system - regulates inflamatory responses (glucocorticoids used clinically as anti-inflammatory agents) - Causes breakdown of skeletal muscle for gluconeogenesis - Causes bone catabolism - Affects brain function (mood, memory, learning)
93
What happens when our blood corticosteroids are too high for too long?
Causes Cushings Syndrome (primary hypercortisolism) - Can be causes by taking glucocorticoid drugs, or diseases that result in excess cortisol, ACTH or CRH - Causes changes in carb and protein metabolism, hyperglycemias, hypertension, muscle weakness - Metabolic problems gives rise to puffy appearance, CNS disorders (depression, decreased learning and memory etc)
94
What is secondary hypercortisolism or cushing disease rather then cushings syndrome?
- Pituitary dependent ie tumour in pituitary gland makes large amounts of ACTH, causing adrenals to make excess cortisol other one syndrome has lower ACTH
95
How does one treat Cushings disease?
- Surgically remove pituitary or adrenal gland - Medical management of signs and symptoms (eg insulin for diabetes, anti-hypertensives for BP, etc) - If not treated, disease worsens, overall health can deteriorate (especially worsening diabetes and high BP which can lead to stroke or MI) myocardial infarction)
96
What happens when cortisol is too low?
Addisons Disease (primary hypocortisolism) - Adrenal insuffiency - Many causes (genetic, autoimmune destrcution of adrenal cortex, etc) - Can be acquired due to high dose steroids given for over 1 week (supresses CRH and ACTH wheich suppresses adrenal glands) - Symptoms include hair loss, blurry vision, abdominal pain, darkening of skin, tremous, depression
97
What does normal adrenal cortisol look like?
Continuous, pulsatile, circadian release
98
More cortisol during sleep time for those who have insomia?
Yes
99
What happens with cortisol when we wake up and right before we go to bed?
Wake up peaks, before bed goes down
100
What is pituitary pars intermedia?
In older horses but has been diagnosed as young as 10 years Cause: - Impaired pituitary (hyperplasia and hypertrophy of pars intermedia middle part of anterior pituitary) - Leads to increased secretion of cortisol by adrenal glands - Results in high blood glucose and supression of immune system What are signs? - Hypertrichosis (excesive hair growth) - Abnormal hair coat including patches of long hair on legs, wavy hair on neck, and changes in coat colour - Muscle atrophy - Excessive sweating - Formation of fat pads on top of neck, tail head and above/around eyes - Pot-bellied appearance
101
How is pituitary pars intermedia dysfunction (PPID) detected?
- Measuring resting (basal) ACTH and fasting insulin Treatment: meds - Acts on pituitary gland to decrease circulating ACTH ex. pergolide Treatment- management - Excercise - Weight loss (if obese) - Limit starch/sugar in diet
102
How does the hypothalamus-pituitary-thyroid axis work?
1. Hypothalamus releases thyrotropin-releasing hormone 2. Down vascular system to anterior pituitary stimulate anterior pituitary to release the thyroid-stimulating hormone 3. Travel down to thyroid gland stimualte secretion of thyroid hormones T3 and T4 (thyroxine) Balanced by negative feedback through thyroxine
103
Where is the thyroid gland located?
Just below the larynx (ie voice box) - on either side of the trachea (lateral to the first 3-8 tracheal rings) 2 lobes are connected by isthmus - Very fibrous in cows and horses - Almost impossible to find in dogs and cats - Largest purely endocrine gland (20-25g)
104
What makes up the thyroid gland?
- Follicles that take up iodide from the blood - In colloid (fluid surrounding follicles) thyroid peroxidase enzyme (TPO) helps attach iodide to tyrosine residue in thyroglobulin
105
What is thyroglobulin?
Made by folliular cells - Long peptide chain with lots of tyrosine side chains - Found in colloids - Iodide brough from blood into folliuclar cells by sodium-iodide transporter, then into colloid by transporter called pendrin - TPO (thyroid peroxidase enzyme) removes electron from iodide to produce iodine
106
What are the two types of outcomes for when iodine binds to tyrosine residues?
- Attachment of 1 iodine on tyrosine ring make MIT (monoiodotyrosine) - Attach,ent of 2 iodines on tyrosine ring makes DIT (diiodotyrosine) - Enzymes on colloid modify the strucutres of MIT and DIT, joining them together - Triiodothyroning T3 (MIT+DIT) - Tetraiodothyronine T4 (DIT+DIT)
107
Are T3 and T4 still attached to thyroglobulin backbone?
Yes, then thyorgloulin taken back up by follicular cells and cut, seperating T3 and T4, upon stimulation by TSH - T3 and T4 secreted out to bloodstream (bound to carrier protein) LIPID LOVING need carrier proteins
108
What is the protein carrier of T3 and T4?
TBG
109
Only free fractions of thyroid hormone are biologically active they must lose the carrier protein in able to elicit effects in target cells
yes
110
Travels from T4 in bloodstream then...
must get converted to T3 once in target cells cytoplasm, needs one T3 in nucleus and vitamin a derivative both binds to tre (hormone response element in nucleus) make protein and response
111
How is TRH regulated?
- Pulse secretion of from hypothalamus - Young animals secrete more then older animals - Stress and cold result in increased secretion - Secretion highest in humans between 10 am and 2pm - Thyroid horomones elevate basal metabolic rate (ie resting rate of caloric expenditure by body) - Secretion highest in rodents at night instead of day
112
What do thyroid hormones do in body?
- Elevated basal metabolic rate - Needed for normal gonadal development and function - Needed for normal embryonic/fetal development, particularly for developement of CNS - Production often impaired with age - Deficiency or excess may have bad consequences
113
What is the difference between hypothyrodidism and hyperthyrodisim?
Hypo: - Low basal metaoblic rate - Weight gain, lethargy, intolerance to cold Hyper: - Increase metabolic rate - Weight loss, muscular weakness, nervousness, protruding eyes
114
What are the causes of hypo and hyperthyroidism?
- Insuffucient dietary iodide - Thyroid gland defect - Impaired thyroid hormone pathway - Insiffuence TSH from anterior pituitary - Insufficient TRH from hypothalamius - Mutant TSH or TRH receptors (genetic) - Mutant TH transport proteins - Autoimmunity
115
What is cretinism?
- Deficiency of thyroid hormones - Usually due to innate maternal hypothyroidism, but also from iodine deficiency - Diet defificent in iodine affects many worldwide - Reduced physdical growth and developmental delays - Treatment with thyroxin T4 soon after birth (especially before 1 month of age), completely or almost completely restores mental developmeny by age 5
116
When does tyroid hormone dependent brain development begin?
In utero and is completed after birth - Important for dendritic and axonal growth, myeling formationm and synapse formation - Important for neural migration - Maternal thyroid homrones first supply the needs of the embryo/fetus
117
What are goiters?
Abnormal tyroid growth due to hypothyrodism 1. Low iodide intake reuslts in low thyroid hormone production 2. Low plamsa thyroid hormones results in high TRH 3. High TRH results in high plasms TSH 4. High plasma TSH stimulates excess growth of thyroid Since low thyroid hormones t4 leads to negative feedback loop not working causing it to overproduce
118
What is Graves disease?
Hyperthyoridism - Autoimmune antibodies activate thyorid gland, lkeading to high T3 and T4 - High thyroid concentration leads to low TRH and low TSH - Causes protruding eyes
119
Can you use a one size fits all with problems with the thyroid hormone?
No, since diff from patient to patient
120
What are the symptoms of hyperthyrodism in cats?
- Weight loss - Increased thirst - Increase urination - Increased heart rate - Vomting and diarrhea - Restlsness and hyperactivity - Greasy or matted hair
121
What do you see happen about the thyoird in dogs primary?
Primary hypothyrodism (destruction of thyroid) 1. Lymphocytic thyroditis (immune filtration); affect 50% doberman pinschers 2. Idiopathic atrophy of thyroid (thyroid tissue lost and replaced by adipose cells)
122
What is secondary hypothyrodism in dogs?
1. thyroid destruction secondary to neoplasia; affects 40% of dogs with cancer (thyroid cancer) 2. Congenital hypothyrodism/crenitism/pituitary dwarfism (conginetal issues) more then 75% of both lobes must be non-functional before developing clinical signs (75% of thyroid must stop working before symptoms appear ex. myxedema (tissue swelling, stupor, coma)
123
How are thyroid disorders treated?
1. Surgery (eg hemithyroidectomy) 2. Hormone supplementation (start with low dose) 3. Radiation therapy (cancer) 4. Blockers (eg thiouracil derivatives and thiocarbamides decrease iodiantion and conversion from t4 to t3) 5. Stimulants (eg furosemide increases conversion from t4 to t3) 6. Diet, electrolyte infusions, etc`
124
How much calcium is found in bones and where is it stored?
99%; stored as hydroxyapatite - Made up of calcium salts and phosphate which allow for structural integrity making them strong
125
Where is the other 1% of calcium found?
In soft tissues; intracellular (0.9%) and extracellular (0.1%) calciu ions essential for several normal biochemical processes (neuromuscular excitation, blood coagulation, hormone secretion, enzyme acitivty, fertilization etc)
126
What are some differences between intracellular and extracellular calcium?
Intracellular (0.9%): - Highly regulated - More abundant - Assoscioated with membranes in mitochondria, ER and plasms membrane Extracellular (0.1%): - Tightly regulated - about 50% ionized (free) - 40% protein bound - 10% complexed with phospahte and citrate
127
How do you calculate the total body calcium?
intake-output
128
What is the intake and output of calcium?
Intake=diet - 1/3 absorbed in small intestine - Absoprtion is hormone regulated - Recommeneded about 1000mg/day Output=kidneys - Body cany make it so has to be replaced
129
What are the 3 hormones that regulate movement of calcium between bone, kidneys, and intestine?
1. Parathyroid hormone (PTH) 2. Calcitriol (vitamin D3) 3. Calcitonin 1 and 2 most important for adults
130
What are some facts about parathyroid?
- PTH is a peptide made by parathyroid gland - PTH is secreted continously (not stored) - PTH helps regulate calcium - Thyroid gland can be surgically removed, but parathyroid gland cannot (needed for life) - Parathyroids seen in terrestrial amphibians onwards first appeared with them and now found in higher animals
131
What are the 2 types of cell types in the parathyroid gland?
1. Chief cells (produce PTH) 2. Oxyphils (function not known) larger
132
What happens when Ca2+ begins to fall?
PTH acts to raise blood Ca2+ back to normal via 3 mechanisms... 1. Stimulates osteoclasts to resrob bone (primary mechanism) 2. Stimulates kidney to resorb Ca2+, (tells kidneys to keep more Ca2+ instead of excreting it) 3. Stimulates kidneys to produce enzyme needed to activate vitamin D, which promotes better absorption of Ca2+ from food/drink across intestinal epilethium (activating vitamin D to help absorb more Ca2+ from food)
133
What increases blood calcium levels?
- Vitamin D3 -PTH Parathyroid
134
What decreases blood calcium levels?
- Calcitonin and thyroid
135
What is the difference between hypocalcaemia and hypercalcaemia
Hypo: increases PTH secretion (stimulates resorption to get more Ca2+ back into blood) Hyper: decreases secretion
136
What are the two types of bone deposition?
Bone resporbption: - Osteoclasts dissolve hydroxyapatite and return the bone Ca2+ (& phosphate) to the blood Bone deposition: - Osteoblasts secrete a matrix of collagen protein, which becomes hardened by deposite of hydroxyapetite
137
What do PTH stimulate kidneys to do?
Stimulates kidneys to reabsorb Ca2+ and produce 1-alpha-hydroxylase enzyme needed to activate vitamin D, vitamin D3 will act on intestine to absorb more Ca2+ fro food/drink
138
How is vitamin D made?
1. Vitamin D3 produced from its precurcor molecules 7-dehydrocholesterol under the influence of UVB sunlight (vitamin D3 comes from 7..., uvb sunlight converts it into previtamin D3, which then becomes vitamin d3) 2. Vitamin D3 secreted into blood from skin/intestine (functions as pre hormone ie inactive) (vitamin d3 enters blood but inactive, transported from skin and intestines into the bloodstream) MUST BE ACTIVATDED BY LIVER AND KIDNEYS 3. Goes to liver and is chemically changed (hydroxyl group added to C25) 4. Requires hydroxyl group addition to C1 to become active (done by enzyme in kidneys stimulated by PTH)
139
What does vitamin D do?
- Stimulates intestinal absoprtion of Ca2+ - Directly stimulates bone resorption by promting promoting formation of osteoclasts
140
What is the difference between humans and dogs and cats with vitamin d3?
Humans: synthesized by 7-dehydrocholsterol with uv light in skin and obtained from dietary sources Dogs and cats: obtained only from diet
141
Does the production of vitamin D in the skin provides most a persons vitamin D
Yes
142
How much vitamin D do food sources provide?
food sources (fortitifed milk, eggs, fish) provide on average only 10-20%
143
At the equoator exposure to sunlight can allow for sufficient cutaneous production of vitamin D3
yes
144
Where is calcitonin made?
- Made in C cells of thyroid in response to high Ca2+ - Thought to play a minor role in adult humans (thyroidectomy patients are not hypercalcaemic)
145
Is phosphate regulated similarily to calcium?
Yes, but not as stirictly, it moves between the bones, kidneys and digestive tract to maintain balance
146
What is the difference between hyperparathyoridism and hypoparathyroidism?
Hyper: - Parathyroid to active - Hypercalcaemia (too much Ca2+) - Increased bone resoprtion (fractures) - Mineralization of soft tissues - Increased thirst and urination (Ca2+ blocks ADH antidiaretic hormone effects) - ADH helps kidneys retain water and produce concentrated urine Blocks ADH from keeping it so releases it Hypo: - Parathyroid not active enough - Hypocalcaemia not enough Ca2+ in blood - Musuclar weakness, ataxia - Cardiac arrythmias
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What does vitamin D defficency cause?
- Poor bone mineralization Children=rickets - bone pain, stunted growth, deformities In adults=osteromalacia - Bone pain, fractures - Soft bones
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What is osteoporosis?
- Most common disorder of the bone - Reduction of bone quality due to excess absoprtion - Risk of bone fractures Known risk factors: - Sex (females, especially after menopause) - Lack of excercise - Calcium deificient diet BONE BREAKDOWN
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Are fractures from osteoporosis more common then heart attack, stroke, and breast cancer combined?
Yes
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How many women and men will have osteoporotic fracture in their lifetime?
Women: 1 in 3 Men: 1 in 5
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What is the treatment for osteoporosis?
- Adequate calcium and vitamin D intake - Hormone therapy, PTH, calcitonin (may be associated with cardiovascular disease, stroke, cancer) - Excercise - Best treatment is prevention - Calcitonin reduces calcium levels by reducing bone breakdown
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What is the somatotropic axis?
Regulates the growth hormone secretion
153
What is GH secretion inhibited by?
GH secretion inhibited by somatostatin from hypothalamus, GHRH stimulates secretion from anterior pituitary, GH has many targets (direct or through stimulation of liver's production of somatomedins (IGF-1) indirectly to produce somatomedins with growth and repair
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What is somatotropin?
Growth hormone
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What is somatotropin?
Protein (191 AA polypeptide) with a half life of 6-20 mins
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Where is somatrotropic cells stored?
Synthesized, stored, and secreted by lateral wings of the anterior pituitary gland
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Where are most somatotropin bound to?
Binding protein (GHBP) but may be transported as free hormone, it is the most abundant anterior pituitary hormone, plays important role in growth
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What are the growth hormone secretion patterns?
- Several, large, 10-30 min pulses/peaks each day (gh released in pulses throughout the day, each lasting 10-30 mins) - Biggest GH peak occurs about 1 hour after you fall asleep (linked to bodys circadian rhythm) - GH levels are highest in childhood and puberty, helping with growth - As you get olfer, GH levels decrease (called somatopause) - GH is why kids often wale up with sore legs, helps bones and muscles grow, sometimes causing discomfort
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What do IGFs rely on?
GH acts on liver to produce IGFs (insulin like growth factors) (IGF-1, IGF-2) - Polypeptides with 40% homology to insulin - IGF-1 mostly travels in blood almost entirely bound to transport proteins (IGF-BPs) - Some IGF-1 transport/binding proteins have an endocrine function (ie there are receptors for these proteins) - GH stimulates the synthesis/release of IGF-1 in other tissues besdies the liver ie difficult to differentiate between direct actions of GH and IGF-1 - GH and IGF-1 appear to exert oppsotie actions in some tissues, suggesting independent roles
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Does IGF-1 increase sensitivty of tissue to insulin?
Yes!; GH does opposite (IGF-1 helps cells use sugar better)
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What are the 3 things the growth hormone does?
1. Liver to release IGF-1, which increases bone and cartilage growth, promotes protein synthesis and growth 2. Adipose tissue: increases fat breakdown and releasing fatty acids for energy 3. Most tissues, reduces glucose meaning bodies relies more on fats for energy
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What is the biggest role of GH?
In children; children have 2 periods of rapid growth: postnatal and puberty - GH stimulates growth of 1. Bone and cartilage 2. Soft tissue - Hypertrophy: increased cell size (size of trophy) - Hyperplasisa: increase cell number
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How does bone growth work?
Bone diameter increase - Growth occuring around the bone - Matrix deposits on outer surface of bone Bone length increase - Growth occuring at epiphyseal plates (near ends of bones) - Epiphyseal plate coontains chondrocytes (columns of collagen-producing cells) - As collagen layer thickens, old cartilage calcififes and chondrocytes dengenerate - Osteoblasts invade and lay bone matrix on top of cartilage base Summary for bone length increase: - Happens at epiphyseal plates (growth plates) near the ends of bones - Chondocytes (cartilage cells) make collagen to help bone grow - Over time old cartilage hardens (calcifies) and chondrocytes die - Osteblasts (bone building cells) replace cartilage with new bone matrix
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Does GH directly stimulate chondrocytes?
YES! GH stimulates production of IGF-1 in liver, IGF-1 helps stimulate chondrocyte and osteoblast acitivty
165
What is pituitary dwarfism?
in growing animals, GH underproduction/decreased sensitivity; small size, juvenile proportions, normal shape but stunted
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What is pygmies?
In growing animals, (laron type dwarfism) decreased responsiveness to GH (receptor deficiency)
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What is alopecia?
In adult animals; thin skin, hair loss (poodles)
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What is cushings syndrome?
Adult animals; increased cortisol inhibits GH synthesis
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What is pituitary gigantism
In growing animals
170
What is acromegaly?
In adult animals; thinking of bones/ joints and skin, enlargement of internal organs (tongue, liver, spleen)
171
What is dwarfism in humans?
Severe GH or GHR deficinecy in children
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What is gigantism in humans
Over secretion of GH in children
173
What is acromegaly?
Over secretion of GH in adults, lengthened jaw, coarse faical features, groeth of hands and feet
174
Who was Andre the Giant
- Wrestler and actor - Gigantism, acrogmegaly - 7'4 - DIed at age 47
175
What is the treamtnet for rHGH (lab made growth hormone)
- Approved by US FDA 2003 to treat children with short stature - Daily injections for about 2 years increased height by 1.3 inches - 22,000/year cost - Glucose intolderance, pancreatitis, and psycholgoical problems surroinding height
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Does growth hormone release glucose and cause reduced insulin levels and does it prefer fat for energy
YES
177
What are some other uses for GH?
- Maintaining msucles mass for those with AIDS - Bodybuilding
178
How are mini cats made?
Selective breeding
179
What are dwarf cats?
- Munchkin genetci mutation - Chondrodsyplasia, short-legged
180
What are teacup cats?
- Dwarf breed, normally proportioned - Severe delay in growth msy cause bone, muscle and other endocrine problems
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What are dogs that are ateliotic?
GH deficiency, smal body - Most toy breeds little
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What are bracycephalic dogs?
Shortened skull bones - Flat face short muzzle (eg boxers)
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What are micromelic dogs?
- Short legs - basset hounds, bulldogs, corgis, daschunds, socttish terriers, shetland sheepdogs
184
Do people thing that GH stops aging?
Maybe slows it, but scientific evidence is weak, many GH products dont work as advertised GH broken down in tummy
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What is a commerical application of GH?
Cattle treated with synthetic GH (growth hormone) - 30% increase in milk - Faster growth - Leaner meat (marbling less fat) - Adverse effects on reproduction? - Adverse effects on humans eating it? - Legal in the USA, illegal in Canada
186
How is proopiomelanocortin (POMC) cut?
- Large protein that acts as a precursour molecule - Gets cut by enzymes called converses to produce functinoal peptisades in the body 1. POMC (parent molecule) - 130 amino acids gets broken down into smaller peptides 2. Key products from POMC cleavage: - ACTH (adrenocorticotropic hormone): stimulates cortisol release from adrenal glands - gamma msh involved in skin pigmentation - alpha msh affects skin colour and appetite regulation - beta msh similar function to alpha - CLIP (corticotropin-like intermediate peptide) function not well understoof - gamma LPH (lipotropin): endorphins, involved in fat metabolism - Enk (enkephalin): pain regulation (acts like opiods)
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What do convertases do?
Cleave POMC; different convertases gives rise to different products
188
How many components are in POMC?
13: Main hormones: 4 postranslational peptides - Melanocyte-stimulating hormones (alpha-MSH, beta-MSH, gamma-MSH) - Adrenocorticotropic hormone (ACTH) 5 Melanocortin receptors: 7 membrane; G-coupled protein receptors - MC1R, MC2R, MC3R, MC4R, MC5R 2 melanocortin antagonists - Agouti, agouti related protein (AGRP) 2 proteins that modulate melanocortin activity - Mahogany, syndican-3 1 opiod peptide (product of POMC but not part of melanocortin system) - beta endorphin (pituitary, blocks pain) DIFF ROLES THEN REST
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Is POMC tissue specific?
Yes, different parts of the body process POMC differently to create different hormones Different cell types make different POMC products - Example; pituitary gland makes ACTH, while while skin produces MSH for pigmentation - One prohormone (POMC) can create multiple hormones that control various body functions (stress, appetite, pain, skin colour) - MUTATIONS IN POMC IS RARE BUT POSSIBLE, which can lead to obesity or pigmentation disorders
190
What does alpha MSH do?
Reduces hunger; if mutated can cause early diabetes
191
What does alpha MSH in skin do?
Affects pigmentation, works on melanocytes (cells that produce melanin); if mutated can ause skin colour changes (eg diff pigmentation in humans or coat colour in animals)
192
Where are MCR produced?
Produced in adrenals, skin, brain, penic etc; penile MCR mutation associated with sexual function/dysfunction
193
Does alpha msh increase dark pigment in skin?
Yes... - Alpha MSH binds to MC1R - Activates signal pathways (G-protein coupled receptors, cAMP, pKA, CREB) - Synthesis of MITF (microphthalmia-associated TF) - Transcription of Tyr and DCT which influence pigmentation
194
What are agouti mice?
- Mutation discovered in 1905 - Mutated gene results in overproduction of Agouti protein - Agouti protein is antagonist to MCR1 in skin - Results in yellow pigmentation - Agouti protein antagonist to MCR4 in brain - Overeating and obesity - Model for obesity, hyperglacaemia, and insulin resistance
195
What makes jaguars black?
6% have condition known as melanism (dominant gene mutation in MC1R) making black
196
How does red hair form?
2 copies of recessive mutation in MC1R protein
197
How does erectile dsyfunction form?
- Linked to MC4R mutations - Alpha msh analogs used to treat erectile dsyfunction - Eg melanotan II - Binds to MC3R and MC4R in the brain to increase sexual function
198
How many lobes does breast gland have?
each gland has 7-10 lobes divided by adipose tissue (fat tissue) - each lobe is made up of smaller lobules
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What do lobules contain?
Alveoli; which make milk - milk goes from alveoli to small tubes (secondary tubles) to larger ducts (mammary ducts) to lactiferous duct to nipple - milk collects in lumen of duct during nursing
200
What stimulates growth of mammary gland and duct growth?
- Placenta secretes estrogen and progesterone which stimulates growth and development of mammary gland, after birth estrogen sectretion decreases, and prolcatin secretion increases; milk productin under control of anterior pituitary - Milk release under control of oxytocin from posterior pituitary
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What types of nutrients does breastmilk contain?
- Proteins (casein, lactalbumin) - Lipids - Carbs (primarily lactose) - Vitamin A, B, D, E - Caclium, iron, zinc, selenium, etc - Immuniglobulin A (IgA) - Hormones, growth factors, chemokines
202
Do scientists fully understand the biological basis of trust?
No
203
Does oxytocin increase behaviour and trust?
yes
204
What is the SRY gene?
- Sex determining region of the Y, found on y chromosome in all animals - It triggers male development by turning embryonic gonads into testes - If no SRY, ovaries develop instead
205
What is the fetus at 6 weeks?
- Bipotential primordium (undifferentiated) - no gender yet
206
What does the female fetus at 10 weeks look like?
- Absense of SRY protein" gonadal tissues develops into ovaries - Absence of testosterone and Sertoli cells, means no MIF, wolffian duct degenerates but mullerian duct presence maintained - Absence of MIF, mullerian duct becomes fallopian tube, uterus and vagina
207
What does the male fetus look like at 10 weeks?
- presence of sry protein, gonadal tissue develops into testes - presence of testerone, mullerian inhibition factor (IMF) made from sertoli cells - MIF means wolfian duct maintained, mullerian duct degenerates - Testosterone causes Wolffian duct to become seminal vesicle, vas deferens, and epididymis
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How do genitalia look like in the first 6 weeks of development?
Both have genital tubercle, urethra folds, urogenital sinus, and labioscrotal swellings
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What does the secretion of testosterone lead to?
Mascunalize the structures... Genital tubercle=penis Urethra folds=penil urethra Labioscrotal swellings= scrotum and prostate
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What happens in absense of testosterone?
Gential tubercle= clitoris Labioscrotal swellings= labia
211
How many CHS do nucleated cells in body have?
46 CHS diploid (22 homologous pairs of autsomes and 1 pair of sex CHS) - Oocytes and sperm each contain half a set (23) chs (haploid) - zygote has unique set of 46 CHS- 1 of each homolgous pair from mother and 1 from father
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What can abnormal SRY recombination cause?
XX male (with SRY on X) XY female (no SRY)
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What are the societal implications of SRY recombination?
1992 olymic games: - gender verification-atheletes with sry gene not permitted to particiapte as females 1996 Olympic - females with sry gene rules as false positive and permitted to particiapte Late 1990s - call for elimination of gender verification due to ineffectiveness and uncertainty of method - supported by american medical association... 2000 olympic - screening eliminated but controversies continue
214
Does testes development need insulin receptors?
Yes three important receptors... 1. Insulin receptor (INSR) 2. Insulin-like growth factor 1 receptor (IGF1R) 3. Insulin receptor related receptor (INSSR)
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What happens when one has XY has SRY gene but mutations in those 3 receptors?
Prevents testes, instead ovaries develop
216
What is sex chromosomal mosaicism?
Condition where a person has two or more different types of cells with different sex chromosomes in their body - ex some cells may have XX, while others have XY or just X - happens 1.5 out of 10,000 births - Spectrum ranges from: - turner sydrome (female with X)
217
What are hermaphrodites? (intersex)
- Have both ovary and testes - Various potential karyotypes - Various degrees of mosaicism - About 1 in 1500-2000 births (0.07-0.05% of children born with atypical genitalia requiring a specialist in sex differentiation
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What are pseudohermaphrodites (intersex)?
Where has external genitalia of one sex but internal organs of other sex - Ex males with a defective 5 alpha reductase gene - Enzyme that turns testosterone into DHT stronger form of test - Without enough DHT male genitalia doesnt fully develop - Baby looks female, but has teste inside at puberty test increases body starts developing male traits (deeper voice, male gential growth, facial hair)
219
What are the intersex social implications in Germany?
- Germany, 2013 - Germany was first country in europe to allow babies with intersex traitd to be registered as neither male nor female at birth - Parents could leave gender blank on birth certificates, creating a new category called intermediate sex - Why to reduce pressure on parents to decide a babys gender - To avoid unnecessary gender assignment surgeries on newborns Criticism of law - some felt it dindt go far enough since 1 in 2000 people are born with intersex traits (didint do enough to protect them)
220
What are the intersex social implications on other countries?
Australia (2011) and New Zealand (2012): people can choose x instead of female or male on passports Bangladesh (2011): added other gender option for passports Nepal (2007): added a third gender option on census forms Pakistan (2011): added third gender option on national id cards India (2009): added a third gender category on voter list Thailand: intersex and transgedner people accepted and even recognized by military - do not have seperate legal status no speical legal protections
221
What are the intersex social implications on canada?
- in 2016 provinval government of ontario changes to way gender is displayed on health cards and drivers licenses - ontario health card no longer displays sex designation - early 2017, ontario drivers license to option to dosplay x as gender idenitifer on drivers licenses - 2018, ontario issued first non binary birth certificate to joshua m ferguson who stated new policy will save lives in trans community
222
What is puberty?
- rapid growth and developwith with earlier more obvious signs in females
223
What does puberty activate?
HPG axis resulting in gonadal maturation - Adolescence: maturation of adult social and cognitive behaviours - coupling of both through interactions of nervous system and gonadal steriod hormones
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What happens to FSH and LH at birth?
High at birth, remaining high for the first 6 motnhs of postnatal life before declining to low levels until puberty - Puberty triggered by increase of LH (not constant) - More pulses=puberty starts - LH secretion is higher at night then day Roles of other hormones: - GnRH (from brain) tells body to release more LH - LH triggers sex hormones production: - Test (boys) - Estrogen - Next more sex hormones= puberty changes
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What is GnRH?
- Hormone that controls puberty and reproduction - Does release steadily, but in pulses Why is it important - triggers puberty, by telling body to release LH and FSH which stimulates test and estorgen If no GnRH do not go through puberty normally and may stay sexually immature How is GnRH used in treamtment? - Only works if given in pulses - steady gnrh wony work since body knows pulses
226
Does puberty start at same time for everyone?
No! diff factors can speed up or delay when happens Genetics: some start ealsier or later based on family traits Environment= higher altitudes can delay it Nutrition: poor diet xan slow puberty, while good nutriton speed up Chronic illness some can delay Hormones and chemicals some people worry that synthetic homrones or environemntal chemicals affect puberty timing Precocious puberty: pubery starts really early age 8 girls and 9 boys
227
What is gametogenesis?
Formation and genetic/phenotypic maturation of gametes
228
What are the 4 phases of gametogenesis?
- First phase is identical in males and females - Distinct differences in last 3 phases in males and females
229
What are the phases of gamterogensis?
1. Extraembryonic primordial germ cells (PGSs) and their migration to the gonads 2. Increase the number of PGCs by mitosis 3. Decrease in chromosomal material by meiosis (lose half their CHS) 4. Structural and functional maturation of gametes (oogenesis/spermatogenesis)
230
What are primordial germ cells?
- Earliest precursor of gametes - Originate outside of the gonads in the hindhut - Migrate into the gonads during early embryonic development
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What is mitosis?
- No recombination - Daughter cells are identical
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What is meiosis?
- Recombo - Daugther cells have reduced ploidy
233
What are homolgous CHS?
- Same CHS number - Inherited from each parent ie 1 paternal, 1 maternal - Allelic differences
234
What are sister chromatids?
- Same CHS - Replicated DNA (copies before division) - Exact copies of a chs before it splits
235
Ploidy?
Diploid: 2 sets of homologous CHS (same CHS number, 1 maternal and 1 paternal) Haploid: 1 set of homologous CHS (1 copy of each number)
236
What is crossing over?
- Exchange of segments between 2 CHS during pachytene (third stage of prophase I in meiosis) stage - Not a purely random process - Occurs at hot spots located based on configurations of proteins that organize the CHS early in meiosis - Occurs within small region of homology between sex CHS (x and y) - Hypermethylation of histone proteins in chromatin indiates sepcific sites where DNA strands break and are repaired after crossing over is complete - Crossing over usually occurs in meiosis - Increases genetic diversity
237
What is cohesion?
- Holds sister chromatids together during division
238
What is condensin?
- Important for chromosomal compaction - Needed for both mitosis and meiosis
239
What are the mature gametes in females and males?
Female: oocyte/egg/ovum Males: spermatozoon (sperm)
240
Where does spermatogenesis occur?
- Occurs in the testes - Indefinite process yielding 4 games per cycle - Process in which spermatozoa are produced by male primordial germ cells by mitosis and meiosis - Initial cells called spermatogonia (stem cells), which yield primary spermatocytes by mitosis
241
What is the difference between leydig cells, Sertoli cells, Epididymis and seminiferous tubes?
Seminiferous: tubes inside the testes where sperm is made Leydig: make testosterone Serology: support and nourish developing sperm Epididymis: stores and matures sperm before release
242
What are spermatogonia?
- Diploid stem cells that give rise to 2 daughter cells - One daughter cell reamins at the basement membrane as a stem cell - Second daughter cell (primary spermatocyte) moves towards the tuble lumen
243
What happens at meiosis in spermatogenesis?
1 meiosis: DNA duplicates and daughter cell splits into 2 new, haploid daughter cells (secondary spermatocytes) 2nd: duplicate chromatids split into 4 daughter cells (spermatids) primary spermatocyte undergoes 2 meitoic divisions to form 4 haploid spermatids
244
What is spermatocytogenesis?
- From spermatogonium to primary and then secondary spermatocyte
245
What is spermatidogensis?
- From secondary spermatocyte to spermatid
246
What is spermiogeneis?
From spermatid to mature, immotile spermatozoon
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What is spermiation?
From mature, immotile spermatozoon to mature, motile spermatozoon
248
What is spermatocytogeneis and the steps?
- Results in formation of spermatocytes possessing half of the normal complement of genetic material Phase 1 (spermatogonial phase) - Type A dark (Ad): stem cells that stay in the testes - Type A pale (Ap): start developing into sperm - Type B: fully committed to becoming sperm Phase 2: - Each primary, diploid spermatocyte duplicates ints DNA and divdies into 2 haploid, secondary spermatocytes by meiosis I
249
What is spermatogenesis and the steps?
- Creation of spermatids from secondary spermatocytes - Secondary spermatocytes rapidly enter meiosis II and divide to produce haploid spermatids - Brevity of this stage means that secondary spermatocytes are rarely seen in histological studies (stage is short!!!)
250
What is spermiogeneis?
- Spermatids form tail by growing microtubles (axoneme) on one of the centrioles (basal body) - Anterior part of the tail (midpiece) thickens due to mitochondrial arranement (energy supply) - DNA undergoes condensation - Tightly packed chromatin is transcriptionally inactive - Golgi apparatus surrounds the condensed nucleus forming the acrosome (helps sperm penetrate egg) - Test removes remaining cytoplasm and organelles (resaudual bodies removed by sertoli cells) - Results in mature by immotile spermatozoa
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What are the phases of spermiogenesis? (maturation)
1. Golgi phase - Small vesicles on the golgi fuse and form proacrosomic granules (stay located on one side of the nucleus) - Centrioles migrate to opposite side of the nucleus - Golgi vesicle fusion continues forming a large acrosomic vesicle with a dense acrosomic granule - PC forms attachment point of flagellum - DC gives rise to flagellum itself 2. Cap phase - Acrosomic vesicle forms caps over one side of nucleus (anterior portion) - Golgi and other cytoplasmic organelles migrate toward distal portion of cell - Flagellum start to form from distal centriole 3. Acrosomal phase - Nucelus beings to elongate - Microtubles are reorganized and form manchette - Neck and annulus form - Flagellum continues to develop 4. Maturation phase - Machette forms post nucelar cap - Mitochondria migrate to posterior side of nucleus and form spiral assembly which defines midpiece - Annulus forms connection between middle and prinicpal pieces of flagellum
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What are the key parts of the spermatozoon-head?
Nucleus: holds compact DNA, shaped for easy movement - oval, flattened, compact, with condensed DNA (disulfide cross-linking; protamines) Acrosome: contains enzymes to help sperm penetrate the egg, membrane vessicles with multiple hydrolytic enzymes - covers the anterior 2/3 of the nucleus - enzymes used for acrosmomal reaction during fertilization Postnuclear cap: membrane component posterior to acrosome Plasms membrane: integrity needed for cell survival and function (protects it and keeps its functional)
253
What are parts of the spermatozoon-flagellum (tail)?
Capitulum: neck that attaches flagellum to head Middle piece: mitochondria sheath in spiral (helix) assembly (high production of ATP) (has mitochondria to produce energy (ATP) for movement Principle piece: major piece of flagellum; important for movement Terminal piece: end of microtuble fibers Plasma membrane: covers all segments
254
How does sperm get released?
- Release of mature spermatozoa from sertoli cells into the lumen of the seminiferous tuble - Mature, immotile speratozoa transported to the epididymis in testicular fluid secreted by sertoli cells with the aid of peristaltic contrations Summary: go from sertoli cells into lumen of seminiferous tuble, then to epididymis
255
How many stem cells migrate to embryonic testes?
About 1000-2000 stem cells; therefore meiosis is crucial to produce to produce sperm throughout adult life - Median ejaculation (50th percentile) contains about 255 million sperm in 1.5-5 millilitres of seminal fluid
256
What is oligospermia?
low sperm count; less then 20 million sperm/ml - Lead to decreased fertility
257
How many hours can spermatozoa survive after ejaculation?
Only able to surive for around 80 hours after ejaculation - Female cervical mucus helps to maintain metabolic requirements of spermatozoa - When migrating in genital tract, spermatozoa are seperting from seminal plasms, and resuspended in female genital fluid - Spermatozoa undergo capacitation during passage through female reproductive tract (become fully able to fertilize egg)
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Do only a few sperm reach the site of fertilization?
YES - most sperm eliminated at selective barriers (cervix and uterotubal junction) - Majority of sperm removed by phagocyotis - Damaged/immotile sperm carried back to cervix by ciliated cells (outside)
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What do sertoli cells do?
Structural and metabolic support - maintain environment and protect spermatids from immune system through: - Blood- testis barrier - FAS-ligand (binds to FAS-receptor on T cells, triggers apoptosis of T-cells, and prevents immune attack in developing sperm) -Phagocytose residual cytoplasm -Secrete: - Supporting testicular fluid - Substances that initiate meiosis - ABP (concentrates test in close proximity to developing gametes) (keeps test near sperm for development) - Hormones affecting pituitary gland in control of spermatogenesis (eg inhibin)
260
What is the anatomy of male?
Seminterferous tubules Rete testis Efferent ductules Epididymis (head, body, tail) Ductus vas deferens Ejaculatory duct Urethra
261
What does the hypothalamic-pituitary gonadal axis (male prdocue) from testes?
1: sperm (supported by Sertoli cells) 2: test (leydig cells) darker like males
262
What are the hormones in the hypothalamic pituitary gonadal axis? (HPG axis)
GnRH= gonadotropin releasing hormone secreted into portal vessels FSH= follicle stimulating hormone (gonadotropin) targets sertoli LH= luteinizing hormone (gonadotropin) targets leydig cells LL - Test will travel to other target cells, resulting in development of secondary sex characteristics
263
How does the negative feedback loop work in the reproductive system?
Negative feedback loop helps to maintain hormone levels to maintain balance 1. Test regulation: - hypothalamus releases GnRH triggerd anterior pituitary to relese FSH and LH - LH stimulates leydig cells to produce test - High test levels signal hypothalamus and anterior pituitary to reduce GnRH and LH production - Prevents excessive test levels 2. FSH regulation (via inhibin) - FSH stimulates sertoli cells to support sperm production - Sertoli cells also release inhibin which reduces FSH release from pituitary LH is NOT affected by inhiin so test production can still continue
264
What happenned to Eunuchs?
they were castrated men who were used as royal servants since they were seen as less threatening - Castration was a punishment for sex offenders as early as 200 BC - 700 AD: testes extracts was used to treat impotence (erectile dysfunction) - 1869: watery testes extracts were beleived to boost maculinity (virtility) - 1935: scientists finally isolated test, understanding that it was the key male sex hormone
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Where is test made?
- Secreted by Leydig cells, located between seminiferous tubles (beginning of tract)
266
What does test in fetus do?
Masculinizes tract and external genitalia
267
What does test during puberty and adulthood?
- Growth, maturation, and maintenance of male reproductive system - Libido - Secondary sex characteristics (hair growth, voice, skin, body shape) - Bone, muscle - Brain (behaviour, cognition)
268
What does anabolic steriods do?
- Increased risk of infertility - Mimic the effects of test - Excess test shuts down pathway - Testes stop producing sperm - Testes stop producing test - Decreased libido and fertility
269
How do steroid affect male sperm?
- Steriod users had less LH and FSH - Leading to reduced sperm production and lower natural test - After stopping steroids, hormone levels remianed low for 3-6 months - One year after stopping, hormone levels were similar to non-users, but sperm count took longer to recover - Steroid users often needed medical treatment to restore fertility
270
What does the study for male contraceptives mean?
- Combo of progestin and an adrogen - When the injection was given every 6 months, some participants sperm production recovered earlier than expected - When given every 4 months, no escape meaning better supression of sperm production - First study to test this type of male contraception - Combo effecitvely supresses sperm production, is safe for the short term, and allows sperm production to return to normal after stopping the treatment
271
What is the difference between flaccid state and errect state?
Flaccid (not errect): - Corpus cavernosum (spongy erectile tissue) not filled with blood - Blow flow minimal, and veins remain open, allowing blood to drain out Erect state: - corpus cavernosum fills with blood, causing penis to expand and harden - Arteries widen to increase blood flow, while veins get compressed, reducing blood drainage - Urethra is slightly compressed which helps with ejaculation
272
What does hemodynamic in erection?
- Process that involves changes in blood flow and pressure
273
How does erection happen?
1. Parasympathetic nerves cause arterioles to widen by relaxing smooth muscle 2. Allows more blood to flow into the corpus cavernosum (spongy tissue inside the penis) 3. Veins contract, reducing bloodoutflow which helps maintain the ercetion 4.Increased pressure inside the corpus caernosum leads to erection -k Neurptransmitter nitric oxide
274
Role of nitric oxide in erection?
- NO released and activates enzyme (guanylate cyclase) in smooth muscle cells produces cGMP (singallng molecule) - cGMP lowers calcium (Ca2+) levels, causes smooth muscle cells to relax - Relaxed msucle cells allow blood vessels to widen (vasodilation) increasing blood flow and leading to penis errecton - Triggers msucle relxation, which increases blood flow and cases an erection
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What does viagra do?
Sildenafil (Pfizer) - First tested on humans in 1991 - Was ineffective at first first treated to treat angina (chest pain) but didnt work - During trials patietns reported unexpected erections - Pfizer then tested it for erectile dsyfunction and it worked - Viagra became the first approved drug for erectile dsydunction in 1998 and still used today 7 years later ronaldo
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What is the viagra mechanism of action?
- Blocks enzyme (PDE) that normally breals down cGMP (needed to stimulate erection) - cGMP helps relax smooth muscle, increasing blood flow - More cGMP means better muscle relaxtion, leading to erection
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What are the main parts of the female reproductive anatomy?
- Broad ligament - Ovaries - Oviducts - Uterus - Cervix - Vagina
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What makes up broad ligament?
- It is the folding of the peritoneum (mesothelium and connective tissue) Parts: 1. Mesoovarium (ovaries) 2. Mesosalpinx (oviducts) 3. Mesometrium (uterus, cervix) What is the function? - Supports hangs several anatomical components of reproductive tract (holds and supports reproductive organs) - Prevents friction - Houses vascular supply, lymphatics and nerves
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What do ovaries do?
- Glandular organs that house female gametes surrounded by ovarian follicles Anatomy: 1. Tunica albuginea (outer connective tissue) 2. Cortex (houses follicles and corpus luteum (hormones) 3. Medulla (houses vaculature, lymphatics and nerves) Function: 1. Production of oocytes (oogenesis) 2. Development of ovarian follicles (folliculogenesis) 3. Production of hormones (estradiol and progesterone)
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What do oviducts do?
Tubes connect the ovaries to uterus and help transport egg, sperm and embryos Infundibulum: captures egg after ovulation (fun time captures egg so much fun!) Ampulla: where fertilization happens Isthmus: help transport sperm and can store them Also called follopian tubes, uterine tubes or salpinges
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What does the uterus do?
- Hollow, pear shaped muscular organ in pelvic cavity Anatomy: 1. Endometrium 2. Myometrium 3. Perimetrium Function: 1. Site of embryo implantation and growth 2. Sperm transportation 3. Responsive to hormones (contractions) 4. Prostaglanding secretion (luteolysis) (drop in progesterone pp)
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What does the cervix do?
- Muscular tunnel-like organ located at lower, narrow end of uterus Anatomy: 1. Endocervix 2. Ectocervix (thicker) 3. Os 4. Cervical folds and crypts Function: - Barrier for uterine protection (safe from infections since at base) - Mucus production - Non-pregnant: lubrication and facilitate sperm motility - Pregnant: mucous plug seal pregnancy
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What does vagina do?
- Elastic, muscular canal of 7-10 cm in legnth that serves as an entrance to female reproductive tract Anatomy: 1. Cranial region (secretes mucous) 2. Caudal region (protects) Function: - Copulatory organ (involved in sex reproduction, specifically in the transfer of sperm from male to female) - Birth canal - Mucus production for lubrication - Low pH (3.8-4.5)- micorenvironment regulation (microorganisms needed to prevent infection and sperm prevention (selection))
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What does the vulva do?
1. Provides anatomical closure to vagina 2. Minimize entry of foreign materials 3. Clitoris: highly erectile tissue, similar to penis - Corpus cavernosum (secrete mucous and relax with NO)
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What is the difference between the mature gamete and mature gonad?
Gamete: egg Gonad: ovaries
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How do the hormones in female reproductive tract get regulated?
hormones from the brain (hypothalamus and pituitary) and ovaries
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What does it mean when two cycles occur simulataneously?
Ovarian cycle: - Series of changes in ovary including follicle maturation, ovulation and corpus luteum formation= folliculogenesis Menstrual Cycle (uterine cycle) - Series of changes in hormone production and uterus structure that make pregnancy possible=uterine cycle
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What are the ovarian follicles? pre ovulatory
Supportive structure that secrete a variety or hormones - Made up of mutiple cell types that proliferate upon stimulation for HPG axis - Protect oocyte from environment, provide nutrition and biochemical support - Contribute to oocyte maturation - Folliculogenesis=follucilar phase of ovarian cycle
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What is the difference between primoridal follicle, primary follicle, secondary, antral follicle?
Primordial: single layer of flat cells surrounding oocyte, represent ovarian reserve (smallest, dormant) Primary: starts growing and developingl single layer of cubodial cells surrounding oocytes; makes estradiol (E2)!!! Secondary follicle: 2-3 layers of cubodial cells surrounding oocytes; produced E2 Antral: antrum: fluid filled cavity (E2) - Dependent of LH and FSH (also called tertiary or Graffian follicles); right before ovulation; fluid filled causes it to burst - Only one dominant follicle will release an egg during ovulation; others break down
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What happens in corpus hemorrhagic and corpus luteum and corpus albicans?
Hemorrhagic: - Initial corpus structure - Bloody from rupture vessles (can feel burst) - right after the follicle bursts Luteum: - Structure comprised of luteal cells -Secretes prgesterone (P4) to maintain pregnancy - If no fertilization, goes away - Empty follicle turns into this to prepare for pregnancy Albicans: - In absesne of pregnancy, corpus leteum regresses into white small structure -Eventually disintegrates
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What is the structure and function of the antral follicles?
Structure: 1. Theca externa 2. Theca interna 3. Granulosa cells 4. Cumulus-oocyte complex Function: - Makes estadiol (E2) regulates ovarian and uterine cycles - Houses and protect the maturing oocyte
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What is the difference between theca externa, interna and granulosa cells?
Externa: - Loose connective tissue - Surrounds and supports follicle Interna (like internal test in bal): - Just beneath the theca externa - LH receptors!!!! LI - Produce andorgens (test) (theca outer) Granulosa cells: - Mural granulosa cells line inner part of basal lamina FSH receptors!!!!!! GF - Convert androgens into estradiol (E2)
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What makes up corpus luteum?
- blood vessels make up about 50% of volume - luteal cells make up 30% - reminaing 20% (pericytes, firbocytes, nerves, immune and smooth muscle cells) - High proliferatoin and activty of cells - Luteal cells make progesterone
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How is progesterone synthesized?
1. Trasnported using - Low density lipoporteins (LDL) - High density lipoproteins (HDL) 2. Luteal cells express LH receptors 3. Activates adenylyl cyclase 4. Converts ATP to cAMP 5. Activates protein kinases - enhance internalization - acitvates cholesterase - activates StAR protein 6. Cholesterol converted to pregnenolone 7. Pregnenolone converted to progesterone (P4) Progesterone is made from cholesterol (carried in LDL and HDL) - Luteal cells have LH receptors LH (luteinzing hormone) binds to them - LH activates signalling patheay in cell Luteal cells have LH receptors!!!; mediate cholesterol from pregnelone to prgesterone
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How does reproduction get regulated?
HPG axis 1. Hypothalmus 2. Pituitary gland 3. Gonads 1. Hypothalamus secretes GnRH to pituitary gland 2. Pituitary gland releases FSH and LH (gpnadotropins) into the systemic circulation 3. LH and FSH reach ovaries (ovarian follicle and CL corpul luteum cells have LH and FSH receptors) 4. Ovaries make E2 (follicular phase) or P4 (luteal phase) 5. Feedback mechanisms mediate endocrine response
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What does follicle-stimulating hormone do?
Stimulate the growth and proliferation of granulosa cells in ovarian follicles - Stimulates production of FSH receptors on granuloma cells - Results in increase senstivity to FSH - Less FSH needed to stimulate selected follicles - Stimulates aromatase production and increased enzymativ activity in granulma cells (converts test to estradiol)
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What does LH do?
Luteinzing hormone - Stimulates theca interna to produce test - Test diffuses into GC - Stimulates production of LH receptors on outer GCs - Results in oocyte meisosi resumption!!!!!! - High concetrations after LH surge - Weakens follicle walls and collapse folllicle=ovulation! - Undeces formation of corpus luteum
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pls explain the process of endocrine control of estradiol production?
1. GnRH from hypothalamus to piuitary gland 2. LH and FSH get released from pituitary gland 3. Theca cells - LH binds to them - Makes test 4. Granulosa cells - FSH binds GCs recruitment of aromatase - Make test to estradiol
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How does estradiol work?
- Estradiol main estrogen secreted by follicles into the ovaries - E2 stimulates production of FSH recepotrs (inreased sensitivity to FSH) - E2 stimulates production of LH receptors - Establishes dominant follicle - Increased E2 in the antral follicle induces positive feedback in the pituitary gland - Regulates ovulation - Increased E2 during dominaint follicle stage induces an LH surge 2 days before ovulation - LH surge changed follicle structure, weaking follicle walls and increasing antral pressure - Follicle ruptures, releasing the cumulus oocyte complex
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What happens in the luteal phase?
- LH surge converts remaining granulosa and theca cells into luteal cells= luteinization - Luteal cells make P4 and E2 sustains endometrium development - P4 stimualtes endometrial gland secretions while E2 stimulates spiral artery development
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What happens when there is no implantation?
- P4 and E2 levels decrease causing menstration - Menstural discharge around 80 mL of blood, fluid and cell debris from upper layer of endometrium expoulses from uterus - Overt meses: endometrial spiral arteries responsible for menstral bleeding (primates); like overies humans - Covert menses: endometruim shed without bleeidng due to lack of endomterial spiral artieres (other mammals): estrus cycle
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What does the ovarian cycle do vs the uterine cycle?
Ovarian cycle controls egg development and hormone production, and uterine cycle prepares the womb for pregnancy E2 builds up lining and P4 maintains it
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What are the 3 stages in the uterine cycle?
1. Proliferative phase - Occurs during follicular phase - Increased E2 stimulates growth of endometrium - Before ovulation 2. Secretory phase: - Occurs in luteal phase - Increased P4 from corpus luteum stimualtes development of uterine glands - Endometrium grows in thickness due to E2 and P4 - Makes lining thicker due to E2 and P4 - Uterus prepares for possible pregnancy 3. Mensrual phase: - Necrosis and sloughing of endometrium - Result of decrease in ovarian hormone secretion (e2 and p) during late luteal phase
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What is PMS linked to?
- Linked to luteal phase (after ovulation, before menstruation) - Needs ovulation and corpus luteum formation - Hormone changes affect serotonin, brain chemical linked to mood Goes away with: - Menopause
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How do birth control pills work?
- Synthetic estrogen and progesterone 1. Override the system with high connetration of ovarian hormones 2. Negstive feedback inhibtion of pituitary secretions 3. No LH surge means ovulation never occurs - Stimulates a false luteal phase
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What happens during menopause?
- Estrogen important for cardiovascular health, bone health and behaviour - At menopuase, ovaries are depleted of follicles and stop secreting estrogen (they change at ovarian level not pituiary level) - Menopause associated with increased risk of osteoporosis, hot flashes, and aging - Weak form of estrogen (estriol) made in adipose tissue (females with more adipose tissue have higher elvels or estorgen and are at less risk of osteoporosis) (fat tissue)
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What is the difference between folliculogenesis and oogenesis?
Folliculogenesis: the continuous process of developing a follicle (small sac in the ovary) that holds an egg. it happens in cycles, leading to ovulation; happens every cycle and prepares egg for ovulation Oogenesis: the discontinous process of developing an egg (ovum) starts before birth, but pauses at different stages, completing only when fertilization occurs; oogenesis is a longer process that starts in fetal life, pauses, and only finishes if fertilization happens (develops a mature egg)
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What is oogenesis?
- Formation and genotypic maturation of female gametes - Oogenesis beginds during embryoinc development of the female and continues throughout her lifetime - Oocytes develop a complex cytoplasm during maturation - Completion results in an ovum that sustains embryonic development
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What is oocyte structure?
COC= cumulus oocyte complex Cortical Granules (multiple grand gesture) - Enzymes preventing polyspermy (multiple sperm fertilizing the egg) Zona Pellucida - Protective membrane - Faciliates sperm binding Corona radiata - Cumulus granulosa cells surrouding the oocyte - Intensive crosstalk with oocyte- coordinate oocyte development - Mediated by gap functions
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What does cytoplasm do in the egg?
Cytoplasm provides nourishment to the embryo-> vitellus or yolk - Conserve nutrients and minimize waste, only genetic material is extruded with polar bodies - Asymmetric cell division - Ensures cytoplasm is conserved - Sustains early embryonic development until implantation in the uterus
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Why does unequal cell division happen?
In oocytes due to off-center spindle positining - Results in one large cell (oocyte) and one small polar body - Oocyte keeps most of the cytoplasm to support future embryo development Timeline: - GV to GVBD to MI to PB1 to CSF arrest MII (stages of meiosis)
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Why are mammalian eggs small?
Small since they dont need to store extra nutrients for development (get from mother)
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What are steps of oogenesis?
1. Oocytogenesis - Mitotic divsions resulting in more oogonia - Occurs during embryonic development 2. Ootidogenesis: - First meitotic divison - Results in secondary oocyte and polar body - Occurs after puberty, cyclically 3. Oogenesis: - Completes second meiotic division - Results in mature ovum and two polar bodies - Occurs after fertilization in mammals
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Where does meosis 1 and 2 stop?
- Meiosis I stops at Prophase I - Happens before birth (during fetal development) - Primary oocyte stays frozen in Prophase I until puberty - Meiosis I resumes and completes at ovulation - Just before ovulation primary oocyte finshes meisosi I, forming secondary oocyte and a polar body - secondary oocyte is frozen in metaphase II until fertilization occurs - meiosis II only completes if fertilization happens
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What is a zygote?
Fertilzed egg
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What is ooytogenesis?
- Mitosis of oogonia and differentiation into primary oocytes 1. Oogonia in the differentiating ovary divide by mitosis - mitotic divisions determine the size of ovarian reserve 2. Mitosis continues until formation of primoridal follicles 3. Oogonia differentiate into primary oocytes - Divide through mitosis before birth - Determines the number of eggs a female will have for life - Mitosis continues until primoridal follicles (egg containing structures form) - Oogonia then develops into primary oocyte which pause in prophase I until puberty
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What is ootidogenesis?
- Primary oocytes undergo meiosis I to make a secondary oocyte and polar body Embryonic phase - Onset of meiosis I and nuclear arrest of primary oocytes Adult phase: - Resumption of meiosis I, resulting in secondary oocyte
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What happens during ootidogenesis: embryonic phase?
During embryonic development.. 1. Primary oocytes develop a germinal vesicle (GV) 2. Primary oocytes enter meiosis I 3. Meiosis I arrested at the diplotene stage of Prophase I - All primary oocytes are arrested in Prophase I at birth - purpose of nuclear arrest to protect DNA from damage
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What happens in ootidogenesis-adulthood?
Onset of puberty: 1. Formation of zona pellucida (ZP) - Covers and protects the entire oocyte - ZP proteins important for fertilization 2. Formation of gap junctions - Cytoplasms communication that corsses the zona pellucida - Crtiical for commuinication between the oocyte and granuloa cells (GC) 3. Oocytes undergo growth of cytoplasm volume and cytoplasmic maturation 4. Oocytes arrested at prophase I resume and complete meiosis I
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When does meisis I begin again?
After LH surge - High LH concentration stimulates LH recepotors on mural GCs What happens with a deterioration of gap junctions? - reduction of oocyte cAMP - deactivation of kinases - activation of MPF
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What happens before LH surge?
1. Gap junction breakdown? Granulosa cells send cGMP into oocyte through gap junctions - cGMP inhibits PDE3A which keeps cAMP levels high and prevents meiosis from resuming - LH signalling cuases gap junctions to deteriorate,reducing the transfer of cGMP into the oocyte 2. Loss of cGMP leads to cAMP breakdown - Less cGMP, PDE3A is activated, which breaks down cAMP - Since high cAMP levels were keeping the oocyte in Prophase I, their drop triggers meiosis to resume 3. Activation of MPF (maturation promoting factor) - drop in cAMP allows MPF (maturation promoting factor) to activate, which pushes the oocyte past prophase I into metaphase II (preparing for ovultation)
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What is needed for meiosis resumption?
Loss of gap junctions; gap junctions allow the cGMP to come in
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What helps meiotic resumption?
1. Crossing Over (during meosis I) Segments of one CHS crossingover to a homologous CHS - Results in a random assortment of DNA segments between chromatids - Ensures genetic diversity in daughter cells 2. Completion of meisois I - Asymetric cytoplasmic divsion - extrusion of 1st polar body
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What is oogenensis?
- Characterized by continuation of meosis II and nucelar arrest of secondary oocytes - Ovulation arrested at the metaphase II stage
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What is the difference between the oocyte and ovum?
Oocyte: not fertilized Ovum: fertilized
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What are mature gametes in males and females?
- Spermatozoon - Oocyte structure
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What are mature gonads?
Male: testes Female: ovaries
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How is sperm transported in male?
- Non-motile, infertile sperm passively transported to epididymis for spermiation Duration: 4-12 days - Upon ejaculation, sperm in seminal fluid pass through ducts deferens and mix wth secretions 1. Secretions from seminal vesicles (fructose and prostaglandins) 2. Prostate gland (citric acid, acid phosphate, zinc and magnesium ions) - Sperm starts in testes but isnt motile yet - Moves into the epidymid where matures (4-12 days) - During ejaculation sperm travels through ductus deferenc and mixes with fluids from
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Where sperm is deposited?
Uterus: horses, dogs, pigs, rodents Cervix: pigs and horses Vagina: cows, sheep, cats, rabbits, humans
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How is sperm transported in the female?
1. Sperm deposited in upper vagina (rapid elevation of pH to increase survival) 2. Passage through cervix (fast and slow phases) 3. Passage through uterus/uterine horns 4. Entry into oviducts, where fertilization occurs 5. Passage up ovidcuts by flagllar movement and contractions of oviducts
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What does the pH go from during sperm transport in the upper vagina?
pH goes from 4.3 to 7.2 in 10 seconds (only lasts for few mins enough for pserm to approach cervix at a pH of 6-6.5 optical for sperm motility)
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What is the dual function of the cervix?
1. Major barrier to spermatozoa - Cervical cells secrete mucous - Viscous and gelatinous- inhabitable for sperm - Cervical rings and folds inhibit sperm travel 2. Sperm reservoir - Cervical folds and crypts - Sperm get trapped in crypts - Process facilaited by cervical mucus - More sperm in cervical reservoir= more sperm reaching oviduct
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What does sulfomucin do?
Viscous prevents sperm movement
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What does sialomucin do?
watery- faciliates sperm motility
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What is the difference between rapid and slow transport in the cervix?
Rapid: - Sperm penetrate sialmucin - Quickly go through cervical canal - Adided by muscular contraxtions - Reach uterus Slow: - Sperm swim through cerivcal mucus (2-3 mm/hr) - Sequential release - Slow release ensures conties availabilty of sperm to enter oviduct for fertilization - Can laat up to 3 or 4 days after ejaculation - Increases chances of sperm
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How does sperm transport happen in uterus?
1. Sperm moves towards oviducts - Egg releases chemcisl signals (chemoattractants) that help guide sperm - Uterine muscle contrations help push sperm toward the oviducts 2. sperm reaches the utero-tubal junction - Gatway between the uterus and oviducts, where sperm continue their jounrey toward the egg 3. capacitation (final sperm maturation) - sperm undergo changes in female reproductive tract - changes prepare sperm for fertilization and help them pentrate the eggs protective layer (zona pellucida)
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What is capacitation?
- Aleration of glyocprotein surface of sperm under infleunce of female tissue secretions within the reproductive tract which enables zona pellucida penetration (which allow for binding to zona pellucida or oocyte)
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What does the isthmus do?
- Narrowest part of oviduct stores sperm until ovulation, helping regulate fertilization timing 1. Sperm enters oviduct - sperm reach isthmus and attach to oviduct epithelial cells (OECs) 2. Calcium levels drop in sperm - prevents premature activation and keeps sperm in a low-energy state 3. Protein production by oviduct cells - OECs release proteins that stop sperm from undergoing capacitation too early 4. Progesterone at ovulation releases sperm - when ovulation happens, progesterone rises, triggering sperm release from isthmus so they can reach egg
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How does hyperactivation happen in sperm?
1. Caclium channels activate catsper proteins - Before activation: caclium levels in sperm are low, so motility is weak - After activation: progesterone from oviduct and other signals open catsper calcium channels, allowing Ca2+ to enter sperm more calcium stronger it is
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Step by step sperm tranpsortation and selection...
1. Immediate transport (vagina to cervix) - some sperm lost due to - retrograde loss (sperm goes out) - phagocytosis (immune cells attack sperm) - rest enter cervix and uterus 2. Cervix- sperm selection - Privelged pathways allow only the strongest, most motile sperm to pass - Non-motile sperm and abnormal sperm removed - Cervial mucus helps filter out defective sperm 3. Uterus- sperm activation - capicitation (early stage) being preparing for fertilization - More sperm removed by immune cells (phagocytosis) 4. Oviduct (final sperm actication and hyper activation) - capitation is complete sperm gaims ability to fertilize egg - hyperactive mottility beings isthmus 5. Fertilization in the oviduct (ampulla region) - Acrosome reaction occurs, sperm release enzymes to break through eggs layer
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How does infidibulum capture egg?
1. Ovulayion occurs - dominant follicle bursts, releasing the cumulus-oocyte complex (COC) egg surrounded by protective cells 2. Fimbria help capture egg - Fimbria (finger like projections) of the infindibulum sweep the egg into oviduct 3. Cilia guide the egg to the ampulla - once inside the oviduct, cilia move the egg toward the ampulla where fertilization occurs
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What are the steps of fertilization?
1. Sperm arrives 2. Acrosome reaction (enzymes pentetrate eggs layer) 3. Penetratin of zona pellucida 4. Membrane fusion 5. Fusion of nuclei
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Before sperm fertilize the egg what must be done?
Remove the cumulus cells surrounding it Removes by: 1. Hyaluronidase - Found on surface of capacitated sperm - Breaks down cumulus cell using hydrolytic (digestive) action 2. Sperm motility - Use strong movements (hyperactivation) to break apart the cumulus cells
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Where do capacitated sperm bind to?
Bind to zona pellucida proteins - ZP proteins only allow species-species binding - ZP proteins prevent any other sperm to enter ovum after fertilization - Binding to ZP triggers acrosome reaction (which allows pserm to enter the egg)
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What happens in the acrosomal reaction?
1. Membrane fusion - sperm plasma membrane fuses with outer acrosomal membrane 2. Enzyme release - Pores open, relasing acromsomal enzymes such as Acrosin and hyaluronidase that digest the zona pellucida 3. Exposure of fusion proteins - inner acrosomal membrane exposed, allowing sperm to bind directly to egg membrane
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What happens during sperm-oocyte fusion?
- After sperm pentetrate zona pellucida and reach perivitelline space (area between the zona and egg membrane), cortical granules migrate to periphery of oocyte - Oocyte plasms membrane fuses with equatorial segment - Immediate mebrane depolarization and the fertilzing sperm is engulfed - Cortical granules are released into preivitelline space - Sperm nuclear membrane disappers and the nucleus decondenses
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What does membrane depolarization do?
- Fast block of polyspermy - Rapid depolarization of the vitelline membrane - Triggered by influx of Na+ ions from NaK+ pumps - Results in electrical barrier to sperm entry - Temporary and only lasts few mins
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What is the cortical granule reaction?
- Permanent structural change that happens after fertilization - Slow block of polyspermy Relaxed enzymes: - Peroxidases - Harden glycoprotein to form impentetrable layer Glycososaminoglycans - Attract water into the perivitelling space - Fertilization envelope Proteases - Destroy sperm binding sites - Prevents other sperm from binding to ZP proteins
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What are the steps of fertilization and oocyte activation?
1. Sperm capacitation and chemotaxis - Sperm become fully mature and swim toward egg 2. Acrosome reaction - Sperm release digestive enzymes to break through zona pellucida (outer egg layer) 3. Sperm-egg fusion - Sperm bind to egg membrane and release PLC zeta into thr egg - Cortical granukes released to prevent multiple sperm from entering (block to polyspermy) 4. Activation of PLC zeta enzyme - triggers the breakdown of PIP2 into DAG and IP3 (important singalling) 5. Calcium release from ER - IP3 binds to receptors on ER, causing Ca2+ release in egg 6. Egg activation and cell division resumption - Calcium singal activates the egg, allowing it to resume the cell cycle and being embryonic development
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What do calcium waves do?
After fertilization, calcium waves trigger changes in the egg that allow it to resume development and start dividing What happens? 1. Calcium signals activate NAD+ kinase, helps build new cell wall membranes 2. Cyclin (protein that atops cell division) broken down allow meiosis to continue 3. The egg starts making new proteins, copying DNA, and preparing for development - Allows extrusion of second polar body and formation of maternal pronucleas
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What does the completion of meiosis result in?
1. Completion of meiosis results in a female pronucleus 2. Sperm nucelus decondenses to form male pronucleus 3. Sperm centriole forms microtubles that integratr with ovum microtubles, drawing the pronucelei closer 4. Fusion of two pronuclei: - cellular membranes break - chromatin from both intermix beofre condenging into CHS - embryonic development begins
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What is infertility?
- Inability to concieve after one year of unprotected intercourse - Caused by a myriad of endogenous and exogenous factors - Hormones, reproductivr tract developmeny, homeostasis - Epigenetics and genetics - Damage related to disease conditonis ex cancer and its treatment Male infertility: - conditoins affecting spermatogeneiss - Affecting sperm quantity - Sperm quality - Environmental factors - Probelsm with sperm reaching the female reproductive tract Female: - Ovulation disorders - Condtions of uterus - Fallopian tube damage or blockage (prevents fertilization) - Endomteriosis - Priary ovarian insuffiency - Pelvic adhesions (scar tissues blocking egg movement) Affects 1 in 7 couples worldwide
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What is the difference between AI and IVF?
AI (artifical insemination) - Also called intra-uterine inseminatino - Sperm is washed and injected into uterus In-vitro fertilization (IVF) - Ooccytes are harvested and fertilized in lab - Embryo transfered into carrier or surrogate
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What are some types of IVF?
Classic IVF - In-vitro maturation:oocyte maturatoin (FSH, LH, E2) - In-vitro fertilization: incubatr with sperm (18hr) - In-vitro cell culture: incubate with unhatached blastocyst Intracytoplasmic sperm injection (ICSI) - Treatment for severe male factor sterility - perm quality (motility and morpholoy) assessed - Sperm injected into secondary oocyte cytoplasm
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What happens after fertilization?
- Ciliated epithelium of oviduct moves embryo toward uterus - Mammalian cleavage occurd every 12-24 hrs (dividong and gorwing) - End goal: implanatation of the embryo via burrowing into the uterine endometrium - Day 8-9 goes into the uterine lining (blastocyst hatches from zona pellucida the ball of cells)
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What does early embryonic cleavage look like?
In mammals it is a rotational asnchronous cleavage - Initial divisions of zygote to form early embryo - Involves rapid mitotis divsions with no growth pahses - Reulsts in idential daughter cells called blastomeres - Blastomeres become smaller with each division - Blastomeres up to 8-cell stage are totipotent (can still become any cell in body)
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What happens at the 8-cell stage?
- Blastomeres tightly adhere, forming the 16-cell moruka - Embryo is more compact and cells lose individual identity - Mediated by calcium-activated cell adhesion molecules - E-cadherin- a cell adhesion protein present during early embryonic development - Epithet- associates with E-cadherin
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What is the blastocyst structure?
Inner cell mass - Embryoblast - Gap junctions form - Becomes the embryo proper Outer cell mass - Trophoblasy - Tight junctions form - Becomes fetal placental contribution - FOrms other extraembryonic membranes
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How does blastocyst hatching happen?
- Occurs prior to implantation - EMbryo breaks through zona pellucida due to proteases secreted by blastocyst - Inability to hatch is one cause on infertility - Altered zona pellucida - Absence of proteases - Embryos lacking zona pellucida protein leading to premature hatching
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How does implantation work?
Apposition and adherence: - Embryonic pole adjacent to uterine endometrium - Adhesion via cell adhesion molecules - LIF involvement, L-selectin, trophinin Penetration: - Syncytiophoblast, differentiated multinucleated trophoblast cells - Invasive: secrete digestive eznymes, works its way into uterine tissue - Establishes contact with matenral blood vessels Decidual reaction: - Uterine tissue responds to invasion by setting up immunological barrier (the decidua) - Becomes the maternal portion of placenta
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What is gastrulation?
- A process where the bilaminar disc (two-layered embryo) develops into 3 germ layers - Happens by week 3 of development
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What are the bilaminar disc componets?
Epiblast= maternal portion (becomes embryo) Hypoblast=embryonic protion (helps form extra embryonic structures)
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What are the 3 germ layers?
Ectoderm Mesoderm Endoderm
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What is organogenesis?
- Highly complex and convserved developmental process forming internal organs and systems 1. Ectoderm - Intergumentary system (epidermis) - Nervous sytem 2. Mesoderm - Circulatroy - Intergumentary system (dermis) - Muscokeletal - Urogential 3. Endoderm - Digestive - Glandular tissues - Respiratory
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What are some extraembryonic membranes?
Chorion - fetal portion of placenta - gives fetal oxygen and nourishment Amnion - Encloses embryo - Filled with amniotic fluid - Provides physical protection from impacy Yolk sac - Intitial size of blood cell production (hematopoiesis) - Synthesizes a variety of proteins - Primoridal germ cells (PGCs) Allantois - Independent waste storage and repsoriation (non-mammals)
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How do twins work?
Identical (monozygotic twins) - One fertilized egg splits into 2 embryos - depending on when it splits may share of have seperate - Placenta (chorion) and amniotic sac - If split is late (13-15) conjoined twinis fraternal (dizygotic twins)- two seperate eggs fertilized by 2 sperm - each has its own placenta and amniotic sac
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What is ectopic pregnancy?
Happens when a fertilized egg implants on outside of uterus, dangerous and cannot develop Common locations 1. Fallopoain tube most common (ampullar)(80%) 2. Isthmic (5-10%) - implants in narrow part of fallopian 3. Ovary (0.15%-3%) - rare, egg implatns in oveary instead of uterus 4. Cervix - very rare 5. Abdomen (1.3%) 6. Intramural, myometrial, or peritoneal (less then 1) - plants in uterine muscle or other unsuaul 7. Intestinal (2.5%) - implsnts at junctino of fallopian tube and uterus
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What are the stages of prenatal development?
Germinal period: - Fertilization until implantation - Zygote until embryonic disk Embryonic period - Gastrulation until 8th week of pregnancy - Neurulation - Organogenesis Fetal period - From 9th week of pregnancy until parturition - Age of viability 22 to 28 weeks
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Are levels of estrogen and progesterone needed at the beginning of pregnancy?
Yes!
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What happens embryonic cleavage?
- Corpus luteum synthesizes - Progesterone keep endometrium intact - Progesterone, estrogen, inhibin: feedback supression to pituitary
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What happens during implantation?
- Synctiotrophoblast cells synthesize human chrionic gonadtropin (hCG) - Maintains the corteus letuem until week 5-6
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What does the placenta do?
Produces important hormones to support pregnancy hCG: maintans pregnancy in early stages Estriol (E3): helps uterus grow and prepares breasts for milk production Progesterone (P): prevents contractions, keeps cervix closed, and supports milk glands PTHrP: takes calcium from mothers bone for baby CRH: helpsbaby lungs develop
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How do pregnancy tests work?
- Detects hCG (hormone present in urine during early pregnancy) How it works: 1. Urine sample is applied to test 2. If hCG present: two lines appear (pregnant) 3. If none only 1 line
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What happens during labour and parturition?
- Powerful contractoins of the myometrium in the uterus are needed to expel fetus in a sequence of events called labor Uterine contractions mediated by: 1. Oxytocin - Polypeptide hormone - produced in hypothalamas, released by posteiror pituitatary - produced in uterus 2. Prostaglandins - Cyclic fatty acids with paracrine functions - Produced by uterine glands - PGF2 alpha and PGE2
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What happens in childbirth?
1. Fetal hypothalamus releases CRH (corticotropin releasing hormone starts labor) 2. Fetal anterior pituiatry relases ACTH (aderenocorticotropic hormone), which singalds the adrenal glands 3. Fetal adrenal glands release DHEAS and cortisol which prepare body for birth 4. Hormones activate 3 key pathways: - Positve feedback (more contractions) -Uterine sensitivity (makes iuterus respond more to labor hormones) - Oxytocin pstheaay (triggers strong contractions for delivery)
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