Midterm 2! :O Flashcards

Question

Steroid hormone receptors

Answer 1

. Steroid hormone (e.g. estrogen, androgen) transported bound to plasma carrier protein * Lipophilic i.e. they move across plasma membrane 2. Steroid hormone binds cell cytoplasm receptor 3. Translocates to the nucleus, binds to DNA * Acts as a transcription factor 4. Stimulates gene transcription 5. Protein products 6. Response

Answer 2

. Thyroxine (T4) + carrier binding protein 2. T4 → T3 (triiodothyronine) 3. T3 uses binding proteins to enter nucleus 4. Hormone-receptor complex binds DNA 5. New mRNA 6. Protein 7. Response

Answer 3

1. Hypothalamic neuroendocrine cells release hormone 1 (blood vessel) 2. Hormone 1 signals anterior pitutiary cells to secrete hormone 2 3. Hormone 2 signals target tissue 4. a) if target tissue is endocrine, then a third hormone is released that signals another target tissue 5. Tissue response

Answer 4

* Physically connected to the hypothalamus through an infundibulum (stalk) * Whole gland protected by bone * Anterior pituitary/adenohypophysis = endocrine gland * Posterior pituitary /neurohypophysis = extension of neural tissue

Answer 5

stalk that connects the pituitary gland to the hypothalamus

Answer 6

adenohypophysis = endocrine gland

Answer 7

neurohypophysis = extension of neural tissue

Answer 8

Dopamine (PIH) * Inhibits secretion of prolactin Prolactin releasing hormone (PRH) * Stimulates release of prolactin Thyrotropin-releasing hormone (TRH) * Regulates secretion of thyroid stimulating hormone (TSH) Corticotropin-releasing hormone (CRH) * Regulates secretion of adrenocorticotropic hormone (ACTH) Somatostatin (GHIH) * Inhibits secretion of growth hormone (GH) Growth hormone releasing hormone (GHRH) * Stimulates secretion of GH Gonadotropin-releasing hormone (GnRH) * Regulates secretion of gonadotropin-releasing hormones, luteinizing hormone (LH), & follicle stimulating hormone (FSH)

Answer 9

aka "the stress axis", cause its regulated in times of stress ex. being chased by a bear, we want to break the stores and use them for energy 1. stress stimulates release of CRH 2. CRH signals anterior pituitary to secrete ACTH 3. ACTH signals the adrenal gland to release glucocorticoid (cortisol) (and synthesize POMC) 4. Cortisol, by negative feedback inhibition, signals hypothalamus and anterior pituitary to stop secreting their things (CRH & ACTH) and stop making POMC

Answer 10

- glucocorticoid - chronic stress hormone - released by adrenal gland

Answer 11

gland that sits atop the kidneys and releases stress hormones like cortisol

Answer 12

From the hypothalamic paraventricular nucleus Central stimulatory control: * Noradrenergic * Stimulates pre-proCRH gene & protein expression (196 AA) * Processed to CRH (41 AA) * Stimulates pulsatile release of CRH Inhibitory influences: * Physiological levels of cortisol inhibit release of CRH (& possibly inhibit pre- proCRH gene expression)

Answer 13

CRH produced by parvocellular neuroendocrine cells within paraventricular nucleus of hypothalamus

Answer 14

CRH released at median eminence (base of the brain) from neurosecretory nerve terminals, into blood vessels in the hypothalamic-pituitary portal system

Answer 15

1. ACTH – adrenocorticotropic hormone (regulates adrenal cortex function) 2. MSH – melanocyte stimulating hormone (skin pigmentation in response to UV radiation) 3. End – β-endorphin (analgesic roles in central nervous system) 4. Enk: enkephalin (analgesic roles in fetus) 5. MC3,4,5 – receptors (hypothermia, hypotension, feeding behaviour, appetite)

Answer 16

Proopiomelanocortin (POMC) N-terminal peptide that's 130 AA long Convertases: * Enzymes that cleave POMC * Different convertases give rise to different products

Answer 17

Made up of 2 embryologically distinct tissues that merged during development (similar to pituitary): - adrenal cortex - adrenal medulla the adrenal glands sit atop the kidneys

Answer 18

Adrenal cortex = secretes steroids (corticosteroids) * Glucocorticoids (e.g. cortisol) → controlled by ACTH * Mineralocorticoids (e.g. aldosterone) → controlled by renin- angiotensin system * Sex steroids (e.g. testosterone) → controlled by ACTH

Answer 19

Adrenal medulla = modified sympathetic ganglia, secretes catecholamines (e.g. epinephrine) part of adrenal gland

Answer 20

Capsule (top) Cortex: ZOna giomerulosa Zona fassciculata Zona reticularis Medulla

Answer 21

secretes mineralocorticoids first part of the adrenal cortex

Answer 22

second part of the adrenal cortex secretes glucocorticoids

Answer 23

third/last part of the adrenal cortex secretes androgens

Answer 24

epinephrine

Answer 25

Protects against hypoglycemia (low blood sugar) * Promotes gluconeogenesis (increase blood sugar) * Plays a role in immune system * Suppresses immune system * Regulates inflammatory response (glucocorticoids used clinically as anti-inflammatory agents) * Causes breakdown of skeletal muscle for gluconeogenesis * Causes bone catabolism * Affects brain function (mood, memory, learning)

Answer 26

Cushing’s Syndrome (primary hypercortisolism) * Prolonged exposure to high levels of cortisol * Can be caused by taking glucocorticoid drugs, or diseases that result in excess cortisol, ACTH, or CRH * Causes changes in carbohydrate & protein metabolism, hyperglycemia, hypertension, muscular weakness * Metabolic problems give rise to puffy appearance, CNS disorders (depression, decreased learning & memory, etc.)

Answer 27

Pituitary-dependant i.e. a tumour in the pituitary gland produces large amounts of ACTH, causing adrenals to make excess cortisol

Answer 28

Distinguishing between the two: ACTH levels lower in Cushing’s Syndrome

Answer 29

Surgery to remove pituitary or adrenal gland (depending on source) * Medical management of signs & symptoms (e.g. insulin for diabetes, anti- hypertensives for BP, etc.) * If not treated, disease worsens, overall health can deteriorate (especially worsening diabetes & high BP which can lead to stroke or MI)

Answer 30

primary hypocortisolism * Adrenal insufficiency * Many causes (genetic, autoimmune destruction of adrenal cortex, etc.) * Can be acquired due to high-dose steroids given for >1 week (suppresses CRH & ACTH which then suppress adrenal glands)

Answer 31

Continuous, pulsatile, circadian release

Answer 32

pituitary pars intermedia dysfunction Affects older horses but has been diagnosed as young as 10 years Cause: * Impaired pituitary (hyperplasia & hypertrophy of pars intermedia) * Leads to increased secretion of cortisol by adrenal glands * Results in high blood glucose & suppression of immune system

Answer 33

pituitary pars intermedia dysfunction (PPID) Common signs: * Hypertrichosis (excessive hair growth) * Abnormal hair coat including patches of long hair on legs, wavy hair on neck, & changes in coat colour * Muscle atrophy * Excessive sweating * Formation of fat pads on top of neck, tail head, & above/around eyes * Pot-bellied appearance

Answer 34

Diagnosis: * Measure resting (basal) ACTH & fasting insulin Treatment – medication * Acts on pituitary gland to decrease circulating ACTH e.g. Pergolide Treatment – management * Exercise * Weight loss (if obese) * Limit starch/sugar in diet

Answer 35

Just below larynx (i.e. voice box) * On either side of trachea (lateral to the first 3-8 tracheal rings) * 2 lobes connected by isthmus * Very fibrous in cows & horses * Indistinct in dogs & cats * Largest purely endocrine gland (20-25g)

Answer 36

Follicles take up iodide (I-) from blood * In the colloid, thyroid peroxidase enzyme (TPO) helps attach iodide to tyrosine residue in thyroglobulin

Answer 37

thyroid peroxidase enzyme TPO removes an electron from iodide to produce iodine helps attach iodide to tyrosine residue in thyroglobulin

Answer 38

Thyroglobulin is made by follicular cells * Long peptide chain with lots of tyrosine side chains * Found in colloid

Answer 39

It's a transporter used to take Iodide into colloid after it's been brought into follicular cells

Answer 40

Iodine binds tyrosine residues in thyroglobulin; 2 outcomes * Attachment of 1 iodine on a tyrosine ring produces MIT (monoiodotyrosine) * Attachment of 2 iodines on a tyrosine ring produces DIT (diiodotyrosine) * Enzymes in the colloid modify the structures of MIT & DIT, joining them together * Triiodothyronine i.e. T3 (MIT + DIT) * Tetraiodothyronine i.e. T4 (DIT + DIT) - T3 & T4 still attached to thyroglobulin backbone * Thyroglobulin taken back up by follicular cells & cut, separating T3 & T4, upon stimulation by TSH * T3 & T4 secreted out to bloodstream (bound to carrier protein)

Answer 41

>99% of thyroid hormones in blood circulation bound to plasma carrier protein called thyroxin-binding globulin (TBG) * Only free fractions of thyroid hormones are biologically active i.e. must lose carrier protein to elicit effects in target cells

Answer 42

1. Thyroxine (T4) + protein carrier * T4 → T3 (triiodothyronine) * T3 uses binding proteins to enter nucleus * Hormone-receptor complex binds DNA * New mRNA * Protein * Response

Answer 43

- Pulsed secretion of from hypothalamus * Young animals secrete more than older animals * Stress & cold result in increased secretion * Circadian rhythm of thyroid hormones * Secretion highest in humans between 10am – 2pm * Thyroid hormones elevate basal metabolic rate i.e. resting rate of caloric expenditure by body * Secretion highest in rodents at night instead of during the day

Answer 44

Young animals secrete more than older animals * Stress & cold result in increased secretion * Circadian rhythm of thyroid hormones * Secretion highest in humans between 10am – 2pm except for rodents - secretion is highest at night instead of during the day

Answer 45

Elevate basal metabolic rate * Needed for normal gonadal development & function * Needed for normal embryonic/fetal development, particularly for the development of the central nervous system * Production often impaired with age * Deficiency or excess may have serious consequences

Answer 46

Abnormally low basal metabolic rate * Weight gain, lethargy, intolerance to cold

Answer 47

Increased basal metabolic rate * Weight loss, muscular weakness, nervousness, protruding eyes (exophthalmos)

Answer 48

* Insufficient dietary iodide * Thyroid gland defect * Impaired thyroid hormone pathway * Insufficient TSH from anterior pituitary * Insufficient TRH from hypothalamus * Mutant TSH or TRH receptors (genetic) * Mutant TH transport proteins * Autoimmunity

Answer 49

* Congenital (existing since birth) deficiency of thyroid hormones * Usually due to innate maternal hypothyroidism, but may also arise from iodine deficiency * Diet deficient in iodine affects many worldwide i.e. major public health concern in many countries * Reduced physical growth & developmental delays * Treatment with thyroxin (T4) soon after birth (especially before 1 month of age), completely or almost completely restores mental development by age 5

Answer 50

- Thyroid hormone-dependent brain development begins in utero & is completed after birth * Important for dendritic & axonal growth, myelin formation, & synapse formation * Important for neuronal migration * Maternal thyroid hormones first supply the needs of the embryo/fetus

Answer 51

abnormal thyroid growth due to hypothyroidism

Answer 52

1. Low iodide intake results in low thyroid hormone production 2. Low plasma thyroid hormones results in high TRH 3. High TRH results in high plasma TSH 4. High plasma TSH stimulates excess growth of thyroid

Answer 53

- due to hyperthyroidism - Autoimmune antibodies activate thyroid gland, leading to high plasma T3 and T4 * High thyroid hormone concentration leads to low TRH, & subsequently low plasma TSH * Exophthalmia (protruding eyes)

Answer 54

Weight loss despite increased appetite * Increased thirst * Increased urination * Increased heart rate * Vomiting & diarrhea * Restlessness/hyperactivity * Greasy or matted hair

Answer 55

Primary hypothyroidism (usually from destruction of thyroid) 1. Lymphocytic thyroiditis (immune infiltration); affect 50% Doberman Pinschers 2. Idiopathic atrophy of thyroid (thyroid tissue lost & replaced by adipose cells) * Predisposed breeds: Doberman Pinscher, Golden Retriever, Irish Setter, Miniature Schnauzer, Dachshund, Cocker Spaniel, Airedale Terrier

Answer 56

1. Thyroid destruction secondary to neoplasia; affects 40% of dogs with cancer 2. Congenital hypothyroidism/cretinism/pituitary dwarfism * ≥75% of both lobes must be non-functional before developing clinical signs (myxedema i.e. swelling of tissues with severe hypothyroidism, stupor, coma)

Answer 57

1. Surgery (e.g. hemithyroidectomy) 2. Hormone supplementation (start with low dose) 3. Radiation therapy (cancer) 4. Blockers (e.g. thiouracil derivatives & thiocarbamides decrease iodination & conversion from T4 to T3) 5. Stimulants (e.g. furosemide increases conversion from T4 to T3) 6. Diet, electrolyte infusions, etc.

Answer 58

99% of calcium found in bones * Stably stored as hydroxyapatite * Calcium salts + phosphate provide structural integrity 1% of calcium found in soft tissues * Intracellular (0.9%) & extracellular (0.1%) calcium ions essential for several normal biochemical processes (neuromuscular excitation, blood coagulation, hormone secretion, enzyme activity, fertilization, etc.)

Answer 59

that 0.1% ~50% ionized (free) * ~40% protein-bound * ~10% complexed with phosphate & citrate * Extracellular fluid/plasma * Bone

Answer 60

* Also highly regulated * More abundant than extracellular * Largely associated with membranes in mitochondria, endoplasmic reticulum, & plasma membrane

Answer 61

Total body Ca2+ = intake - output Intake = diet * ~1/3 absorbed in small intestine * Absorption is hormone regulated * Recommended ~1000mg/day Output = kidneys * Body can’t make it so it has to be replaced

Answer 62

1. Parathyroid hormone (PTH) 2. Calcitriol (vitamin D3) 3. Calcitonin 1 & 2 most important in adults

Answer 63

PTH is a peptide made by parathyroid gland * PTH secreted continuously (not stored) * PTH helps regulate calcium When plasma Ca2+ begins to fall, PTH acts to raise blood Ca2+ back to normal via 3 mechanisms

Answer 64

It makes PTH Thyroid gland can be surgically removed, but parathyroid cannot (essential for life) * Parathyroids seen in terrestrial amphibians onwards

Answer 65

1. Chief cells (produce PTH) 2. Oxyphils (function unknown)

Answer 66

PTH raises blood Ca2+ back to normal when it's low by: 1. Stimulates osteoclasts to resorb bone (primary mechanism) 2. Stimulates kidneys to resorb Ca2+ and produce 1-α-hydroxylase enzyme needed to activate vitamin D 3. Stimulates kidneys to produce enzyme needed to activate vitamin D, which promotes better absorption of Ca2+ from food/drink across intestinal epithelium

Answer 67

when there's too low Ca2+ PTH secretion increases to get more Ca2+ into blood

Answer 68

when there's too high Ca2+ levels - PTH secretion decreases

Answer 69

Made in C cells of thyroid in response to high Ca2+ * Thought to only play minor role in adult humans (thyroidectomy patients are not hypercalcaemic)

Answer 70

Ca2+ in bone mainly in crystal form (hydroxyapatite), but small fraction is ionized & readily exchangeable Most common form of calcium phosphate is hydroxyapatite Bone is constantly formed & resorbed * Bone contains calcified ECM that forms when calcium phosphate crystals precipitate & attach to a lattice support * Most common form of calcium phosphate is hydroxyapatite * Ca2+ in bone mainly in crystal form (hydroxyapatite), but small fraction is ionized & readily exchangeable

Answer 71

Osteoblasts secrete a matrix of collagen protein, which becomes hardened by deposits of hydroxyapatite

Answer 72

(breaking down of bone) Osteoclasts dissolve hydroxyapatite & return the bone Ca2+ (& phosphate) to the blood

Answer 73

1-α-hydroxylase enzyme formed in the kidney needed to activate vitamin D so Vitamin D3 will act on the intestines to absorb more Ca2+ from food/drink in intestines PTH is what initially stimulates kidney

Answer 74

1. Vitamin D3 produced from its precursor molecule, 7- dehydrocholesterol under the influence of UVB sunlight 2. Vitamin D3 secreted into blood from skin/intestine (functions as a pre-hormone i.e. inactive) 3. Goes to liver & is chemically changed (hydroxyl group added to C25) 4. Requires hydroxyl group addition to C1 to become active (done by enzyme in kidneys that is stimulated by PTH)

Answer 75

Stimulates intestinal absorption of Ca2+ Directly stimulates bone resorption by promoting formation of osteoclasts Humans * Synthesized from 7-dehydrocholesterol with UV light in skin + obtained from dietary sources Dogs & cats * Essential vitamin (obtained only from diet)

Answer 76

Production of vitamin D in the skin provides most of a person’s vitamin D * Food sources (fortified milk, eggs, fish) provide on average only 10-20% * At the Equator, exposure to sunlight can allow for sufficient cutaneous production of vitamin D3 * People living in northern/southern latitudes (including here) have to ingest it in the diet or through supplements

Answer 77

Phosphate metabolism controlled by same mechanisms that regulate Ca2+ metabolism (but not as tightly), to return/receive phosphate to/from bone, kidney filtrate, & GI tract

Answer 78

70% mineral phase - hydroxyapetite (95%) - other components (8%) 30% organic phase - bone matrix 98% (collagen 95%) - bone cells 2% - osteoblases, cytes and clasts

Answer 79

Parathyroid too active * Hypercalcaemia (too much Ca2+ in blood) * Increased bone resorption (fractures) * Mineralization of soft tissues * Increased thirst & urination (Ca2+ blocks ADH effects)

Answer 80

* Parathyroid not active enough * Hypocalcaemia (not enough Ca2+ in blood) * Muscular weakness, ataxia * Cardiac arrhythmias

Answer 81

Results in poor bone mineralization In children = Rickets * Bone pain, stunted growth, deformities In adults = Osteomalacia * Bone pain, fractures

Answer 82

* Most common disorder of bone * Reduction of bone quality due to excess absorption * Risk of bone fractures * Known risk factors: * Sex (females, especially after menopause) * Lack of exercise * Calcium deficient die

Answer 83

- Fractures from osteoporosis more common than heart attack, stroke & breast cancer combined * 1 in 3 women, 1 in 5 men will have an osteoporotic fracture in their lifetime

Answer 84

* Adequate calcium & vitamin D intake * Hormone therapy, PTH, calcitonin (may be associated with cardiovascular disease, stroke, cancer) * Exercise * Best treatment is prevention!

Answer 85

GH secretion inhibited by somatostatin from hypothalamus * GHRH stimulates GH secretion from anterior pituitary * GH has many targets (direct or through stimulation of liver’s production of somatomedins e.g. IGF-1)

Answer 86

aka growth hormone - Protein (191 AA polypeptide) with a half life of 6-20 mins * Synthesized, stored, & secreted by somatotropic cells in the lateral wings of the anterior pituitary gland * Most bound to binding protein (GHBP) but may be transported as free hormone * Most abundant anterior pituitary hormone * Plays an important role in growth

Answer 87

Several, large, 10-30 min pulses/peaks each day * Largest GH peak occurs ~1 hr after onset of sleep (circadian rhythm) * Basal levels highest early in life i.e. amplitude/frequency of peaks greatest during pubertal growth & then decline throughout adult life (somatopause) * Cause of sore legs upon waking as a child

Answer 88

Hyperglycemia (high blood sugar) Glucocorticoids and endocrine disruptors

Answer 89

* GH acts on the liver to produce IGFs (IGF-1, IGF-2) * Polypeptides with 40% homology to insulin * IGF-1 almost entirely bound to transport proteins (IGF-BPs) * Some IGF-1 transport/binding proteins have an endocrine function (i.e. there are receptors for these proteins) * GH stimulates the synthesis/release of IGF-1 in other tissues besides the liver i.e. it is difficult to differentiate between direct actions of GH & IGF-1 * GH & IGF-1 appear to exert opposite actions in some tissues, suggesting independent roles

Answer 90

GH increaases while IGF-1 decreases: - liver glucose release - plasma glucose concentration - Sensitivity of tissue to insulin GH decreases while IGF-1 increases: lipolysis in adipocytes

Answer 91

1. Bone & cartilage 2. Soft tissue * Hypertrophy (increased cell size) * Hyperplasia (increased cell number)

Answer 92

postnatal and puberty

Answer 93

Bone diameter increase - growth occurring around the bone -matrix deposits on the outer surface of bone Bone length increases * Growth occurring at epiphyseal plates (near end of bone) * Epiphyseal plate contains chondrocytes (columns of collagen-producing cells) * As collagen layer thickens, old cartilage calcifies & chondrocytes degenerate * Osteoblasts invade & lay bone matrix on top of cartilage base

Answer 94

GH directly stimulates chondrocytes * GH stimulates production of IGF-1 in liver * IGF-1 helps stimulate chondrocyte & osteoblast activity

Answer 95

Pituitary Dwarfism: small size, juvenile proportions, normal shape at maturity but stunted Pygmies (Laron-Type Dwarfism): decreased responsiveness to GH (receptor deficiency)

Answer 96

Alopecia (dogs): thin skin, hair loss (poodles) Cushing’s Syndrome: increased cortisol inhibits GH synthesis

Answer 97

Pituitary Gigantism

Answer 98

GH over-production in adults thickening of bones/joints & skin, enlargement of internal organs (tongue, liver, spleen)

Answer 99

Severe GH or (GHR) deficiency in children – Dwarfism * Over secretion of GH in children – Gigantism * Over secretion of GH in adults – Acromegaly

Answer 100

* Professional wrestler & actor * Gigantism, acromegaly * 7’4” * Died at age 47 * “Fezzik” in The Princess Bride

Answer 101

* Approved by US FDA in 2003 to treat children with short stature (bottom 1% on growth charts) * Daily injections for ~2 years increased height by 1.3” * $22,000/year cost * Side effects: glucose intolerance, pancreatitis, & psychological problems surrounding height Side effects: glucose intolerance, pancreatitis, & psychological problems surrounding height

Answer 102

Maintaining muscle mass in individuals with AIDS * Bodybuilding/athletic enhancement – controversial!

Answer 103

Miniature * Selective breeding Dwarf * “Munchkin” genetic mutation * Chondrodysplasia, short-legged Teacup * Dwarf breed, normally proportioned * Severe delay in growth may cause bone, muscle, & other endocrine problems

Answer 104

Ateliotic * GH deficiency, uniformly small body * Most “toy” breeds (Chihuahuas, Boston Terriers, Italian Greyhounds, Maltese, Miniature Pinschers, Miniature Spaniels, Pomeranians, Toy Poodles, Yorkies, etc.) Brachycephalic * Shortened skull bones & short muzzle (e.g. Boxers) Micromelic * Short legs * Basset Hounds, Bulldogs, Corgis, Dachshunds, Lhasa Apsos, Scottish Terriers, Shetland Sheepdogs, etc.

Answer 105

Cattle treated with synthetic GH * 30% increase in milk yield * Faster growth * Leaner meat (marbling) * Adverse effects on reproduction? * Adverse effects on humans? * Legal in the USA, illegal in Canada

Answer 106

POMC = proopiomelanocortin A parent molecule 130 AA long Convertases: * Enzymes that cleave POMC * Different convertases give rise to different products

Answer 107

4 posttranslational peptides * Melanocyte-stimulating hormones (α-MSH, β-MSH, γ-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, syndecan-3 1 opioid peptide (product of POMC but not part of melanocortin system) * β-endorphin (pituitary, blocks pain)

Answer 108

Posttranslational processing of POMC is tissue-specific * Different POMC peptides produced by different cell types * Control of range of many physiological functions by same prohormone * Mutations in POMC gene/processing rare but possible

Answer 109

a-MSH produced in brain inhibits food intake * Mutation here results in early onset diabetes

Answer 110

a-MSH produced in skin acts on melanocytes (contain melanin/pigment which influence human skin colour & rodent coat colour) * Mutation here results in altered pigmentation

Answer 111

MCR is produced in adrenals, skin, brain, penis, etc. * Penile MCR mutation associated with sexual function/dysfunction

Answer 112

It increases dark pigment of skin α-MSH binds MC1R * Activates signal pathways (G-protein-coupled receptors, cAMP, PKA, CREB) * Synthesis of MITF (microphthalmia-associated transcription factor) * Transcription of Tyr & DCT which influence pigmentation

Answer 113

* Spontaneous mutation discovered in 1905 * Mutated gene results in overproduction of Agouti protein * Agouti protein is an antagonist to MCR1 in the skin * Results in yellow pigmentation * Agouti protein is an antagonist to MCR4 in the brain * Results in overeating & obesity * Model for adult-onset obesity, hyperglycemia, & insulin resistance

Answer 114

Jaguars usually spotted * 6% have a condition known as melanism (dominant gene mutation in MC1R), making them black

Answer 115

Results from 2 copies of a recessive mutation in the MC1R protein

Answer 116

- Linked to MC4R mutations * α-MSH analogs used to treat erectile dysfunction * E.g. Melanotan II * Binds to MC3R & MC4R in the brain to increase sexual function

Answer 117

7-10 each is divided into lobules

Answer 118

Each gland contains 7-10 lobes divided by adipose tissue * Each lobe is subdivided into lobules * Lobules contain alveoli which secrete milk into secondary tubules * Secondary tubules → mammary ducts → lactiferous duct → nipple * Milk accumulates in lumen of the duct during nursing

Answer 119

Placenta secretes estrogen & progesterone, which also stimulate growth & development of mammary glands & ducts

Answer 120

After birth, ↓estrogen secretion & ↑ prolactin secretion * Milk production under control of prolactin from anterior pituitary

Answer 121

Milk production under control of prolactin from anterior pituitary * Milk release under control of oxytocin from posterior pituitary

Answer 122

* From anterior pituitary * Stimulates milk production * Release triggered by suckling stimulus

Answer 123

* From posterior pituitary * Stimulates milk release * Release stimulated by suckling stimulus, visual/auditory cues (i.e. brain stimuli), or even the thought of the child

Answer 124

* Proteins (casein, lactalbumin) * Lipids * Carbohydrates (primarily lactose) * Vitamin A, B, D, E * Calcium, iron, zinc, selenium, etc. * Immunoglobin A (IgA) * Hormones, growth factors, chemokines

Answer 125

oxytocin plays a role in behaviour & trust

Answer 126

Sex determining region of the Y * Located on the Y chromosome of all animals (highly conserved) * Thought to be important for male determination * Induces embryonic gonads to become testes * Absence of the SRY gene in biological females (lack Y chromosome), results in the development of ovaries

Answer 127

Fetus at 6 weeks * Bipotential primordium (undifferentiated) Fetus at 10 weeks – male 1. Presence of SRY protein → gonadal tissue develops into testes 2. Presence of testosterone → Mullerian inhibition factor (MIF) made from Sertoli cells 3. MIF → Wolffian duct maintained, Mullerian duct degenerates 4. Testosterone causes Wolffian duct to become seminal vesicle, vas deferens, & epididymis

Answer 128

Fetus at 10 weeks – female 1. Absence of SRY protein → gonadal tissue develops into ovaries 2. Absence of testosterone & Sertoli cells → no MIF → Wolffian duct degenerates but Mullerian duct presence maintained 3. Absence of MIF → Mullerian duct becomes the fallopian tube, uterus, & vagina

Answer 129

Males have it: in the presence of testosterone -Mullerian inhibition factor (MIF) made from Sertoli cells MIF causes Wolffian duct to be maintained, and Mullerian duct to degenerate

Answer 130

Essentially identical in males & females during first 6 weeks of development (common urogenital sinus, genital tubercle, urethral folds, & labioscrotal swellings) * Secretions of testes masculinize structures to form penis, penile urethra, prostate, & scrotum * In absence of testosterone, genital tubercle forms clitoris instead of penis & the labioscrotal swellings become the labia majora instead of the scrotum

Answer 131

All nucleated cells in the body except oocytes & sperm contain 46 chromosomes (diploid) * 22 homologous (matched) pairs of autosomes & 1 pair of sex chromosomes Oocytes & sperm each contain half a set of (23) chromosomes (haploid) * Zygote has a unique set of 46 chromosomes – 1 of each homologous pair from mother, & 1 from father Genetic females are XX (one X from each parent) Genetic males are XY (one X from mother & Y from father)

Answer 132

Can result in: * XX male (with SRY on X) * XY female (no SRY)

Answer 133

1992 Olympic games * Gender verification – athletes with SRY gene not permitted to participate as females 1996 Olympic games * Females with SRY gene ruled as “false positives” & permitted to participate Late 1990s * Call for elimination of gender verification due to ineffectiveness & uncertainty of method * Supported by American Medical Association, American Academy of Pediatrics, American College of Physicians, American College of Obstetricians, Endocrine Society, & American Society of Human Genetics 2000 Olympic games * Screening eliminated but controversies continue to this day

Answer 134

important for testes determination - Insulin receptor (INSR) * Insulin-like growth factor 1 receptor (IGF1R) * Insulin receptor-related receptor (INSSR) * XY (SRY present) mice with mutations in all 3 receptors developed ovaries & showed a completely female phenotype

Answer 135

(intersex) Sexual development disorder where individuals have both ovary & testis tissue * Various potential karyotypes * Various degrees of mosaicism * ~1 in 1500-2000 births (0.07-0.05%) of children are born with noticeably atypical genitalia requiring a specialist in sex differentiation

Answer 136

Congenital endocrine disorder * Individual has external genitalia of one sex & internal sex organs of the other sex * E.g. males with a defective 5a-reductase gene

Answer 137

* 5a-reductase converts testosterone to 5-α-dihydrotestosterone (DHT, more potent androgen) * I.e. Normal testosterone but inadequate DHT * Due to inappropriate exposure to androgens during early gestation * Male external genitalia & prostate gland fail to develop fully during fetal development * Born with external genitalia that appears female * Upon onset of puberty, testes secrete testosterone causing masculinization of external genitalia, lower voice, etc.

Answer 138

5-α-dihydrotestosterone (DHT, more potent androgen)

Answer 139

Germany, 2013 * Europe’s first country to allow babies with characteristics of both sexes to be registered as neither male nor female at birth * Parents allowed to leave gender blank on birth certificate, creating new category of “intermediate sex” * Aimed at removing pressure on parents to make quick decisions on sex assignment surgery for newborns * Some said that new law did not go far enough since as many as 1 in 2,000 people have characteristics of both sexes

Answer 140

Australia, 2011 * Option of selecting “X” for gender (indeterminate, unspecified, intersex) on passport applications New Zealand, 2012 * Similar option as Australia Bangladesh, 2011 * “Other” gender category added on passport applications Nepal, 2007 * 3rd gender added on census forms Pakistan, 2011 * Additional option added on national identity cards India, 2009 * 3rd gender category added to voter lists NOT Thailand * While transgender or intersex individuals have long been accepted & are officially recognized by the country’s military, they do not have any separate legal status Canada -

Answer 141

Canada * In 2016 Provincial Government of Ontario announced changes to the way gender is displayed on health cards & driver’s licenses * Ontario health card no longer displays sex designation * In early 2017, Ontario drivers given the option to display “X” as gender identifier on driver’s licenses * In 2018 Ontario issued its first non-binary birth certificate to Joshua M. Ferguson who stated that “the new policy will save lives in the trans community”

Answer 142

Rapid growth & development with earlier, more obvious signs in females * Puberty: activation of the HPG axis resulting in gonadal maturation * Adolescence: maturation of adult social & cognitive behaviours * Coupling of both through interactions between the nervous system & gonadal steroid hormones

Answer 143

↑ FSH & LH at birth, remaining high for the first 6 months of postnatal life before declining to very low levels until puberty * Puberty triggered by ↑ LH (secretion is pulsatile) * ↑ frequency & amplitude of pulses at puberty * Secretion higher at night than during daytime * ↑ GnRH secretion stimulates pulsatile release of LH * ↑ LH results in ↑ sex hormones (testosterone from testes & estradiol from ovaries) * ↑ sex hormone secretion result in development of secondary sex characteristics

Answer 144

Gonadotropin releasing hormone Release occurs in pulses rather than steadily from hypothalamus Triggers release of LH and FSH from anterior pituitary

Answer 145

Children with GnRH deficiency fail to sexually mature * Treatment with GnRH only works if administered in pulses similar to those that occur naturally * Increase in pulsatile GnRH (normally or through treatment) triggers the start of puberty

Answer 146

* Genetic variations in timing of onset (genes not defined) * Environmental factors (e.g. ↑ altitude results in later onset) * Nutrition * Chronic illness * Theoretical concern over synthetic hormones & other environmental chemicals * Precocious puberty (very early onset)

Answer 147

Formation & genetic/phenotypic maturation of gametes * Gametes = haploid i.e. half the number of chromosomes compared to somatic cells in the body * 4 phases of gametogenesis * First phase is identical in males & females * Distinct differences between last 3 phases in males & females

Answer 148

1. Extraembryonic primordial germ cells (PGCs) & their migration to the gonads 2. Increase in the number of PGCs by mitosis 3. Decrease in chromosomal material by meiosis 4. Structural & functional maturation of gametes (oogenesis/spermatogenesis)

Answer 149

Primordial germ cells * Earliest recognizable precursors of gametes * Originate outside of the gonads in the hindgut * Migrate into the gonads during early embryonic development

Answer 150

Crossing Over * Exchange of segments between two chromosomes during pachytene stage * Not a purely random process * Occurs at “hot spots” - location based on configurations of proteins that organize the chromosomes early in meiosis * Occurs within small region of homology between sex chromosomes (X & Y) * Hypermethylation of histone proteins in chromatin indicates specific sites where DNA strands break & are repaired after crossing over is complete

Answer 151

Holds sister chromatids together during division

Answer 152

- Important for chromosomal compaction * Necessary for both mitotic & meiotic divisions

Answer 153

Females: oocyte/egg/ovum Males: spermatozoon (sperm)

Answer 154

- Occurs in the testes * Indefinite process yielding 4 games per cycle * Process in which spermatozoa are produced from male primordial germ cells by mitosis & meiosis * The initial cells are called spermatogonia, which yield primary spermatocytes by mitosis

Answer 155

Theres the epididimus (head, body and tail) ductus deferins - extension of epididimus through which sperm is released therea re Leydig cells and sertolicells

Answer 156

cells we have at start of spermatogenesis diploid stem cells that give rise to 2 daughter cells * One daughter cell remains at the basement membrane as a stem cell * Second daughter cell (primary spermatocyte) moves toward the tubule lumen

Answer 157

1st meiosis: DNA duplicates & daughter cell splits into 2 new, haploid daughter cells (secondary spermatocytes) * 2nd meiosis: duplicate chromatids split into 4 daughter cells (spermatids) * I.e. primary spermatocyte undergoes 2 meiotic divisions to form 4 haploid spermatids

Answer 158

1. Spermatocytogenesis: from spermatogonium to primary & then secondary spermatocyte 2. Spermatidogenesis: from secondary spermatocyte to spermatid 3. Spermiogenesis: from spermatid to mature, immotile spermatozoon 4. Spermiation: from mature, immotile spermatozoon to mature, motile spermatozoon

Answer 159

Male form of gametocytogenesis * Results in the formation of spermatocytes possessing half of the normal complement of genetic material has 2 phases

Answer 160

Phase 1 (spermatogonial phase) * Type A dark (Ad) spermatogonia: stem cells of the seminiferous epithelium * Type A pale (Ap) spermatogonia: committed to differentiation * Type B spermatogonia: differentiated from type A

Answer 161

Each primary, diploid spermatocyte duplicates its DNA & divides into 2 haploid, secondary spermatocytes by meiosis I

Answer 162

* Creation of spermatids from secondary spermatocytes * Secondary spermatocytes rapidly enter meiosis II & divide to produce haploid spermatids * Brevity of this stage means that secondary spermatocytes are rarely seen in histological studies

Answer 163

Spermatids form tail by growing microtubules (axoneme) on one of the centrioles (basal body) * Anterior part of tail (midpiece) thickens due to mitochondrial arrangement (energy supply) * DNA undergoes condensation * Tightly-packed chromatin is transcriptionally inactive * Golgi apparatus surrounds the condensed nucleus forming the acrosome * Testosterone removes the remaining extra cytoplasm & organelles (residual bodies phagocytosed by Sertoli cells) * Results in mature but immotile spermatozoa

Answer 164

1. Golgi phase 2. Cap phase 3. Acrosomal phase 4. Maturation phase

Answer 165

- Small vesicles of the golgi fuse and form proacrosomal granules (stay located on one side of the nucleus) * Centrioles migrate to the 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

Answer 166

* Acrosomic vesicle forms cap over one side of nucleus (anterior portion) * Golgi and other cytoplasmic organelles migrate toward distal portion of cell * Flagellum starts to form from distal centriole

Answer 167

of spermiogenesis - Nucleus begins to elongate * Microtubules are reorganized and form manchette * Neck and annulus formed * Flagellum continues to develop

Answer 168

- Manchette forms post nuclear cap * Mitochondria migrate to posterior side of nucleus and form spiral assembly which defines midpiece * Annulus forms connection between middle and principal pieces of flagellum

Answer 169

Nucleus: oval, flattened, compact, with condensed DNA (disulfide cross-linking; protamines) * Acrosome: membrane vesicle with multiple hydrolytic enzymes * Covers the anterior 2/3 of the nucleus * Enzymes used for acrosomal reaction during fertilization * Postnuclear cap: membrane component posterior to acrosome * Plasma membrane: integrity crucial for cell survival and function

Answer 170

- Capitulum: neck that attaches flagellum to head * Middle piece: mitochondrial sheath in spiral (helix) assembly (high production of ATP) * Principal piece: major piece of flagellum; important for movement * Terminal piece: end of microtubule fibers * Plasma membrane: covers all segments

Answer 171

Release of mature spermatozoa from Sertoli cells into the lumen of the seminiferous tubule * Mature, immotile spermatozoa transported to the epididymis in testicular fluid secreted by Sertoli cells with the aid of peristaltic contractions

Answer 172

Only ~1000-2000 stem cells migrate to the embryonic testes, therefore meiosis is crucial to produce sperm throughout adult life * Median ejaculation (50th percentile) contains ~255 million sperm in 1.5-5.0 millilitres of seminal fluid - Spermatozoa are only able to survive for ~80 hours after ejaculation * Female cervical mucus helps maintain metabolic requirements of spermatozoa * When migrating in genital tract, spermatozoa are rapidly separated from seminal plasma, & are resuspended in the female genital fluid * Spermatozoa undergo capacitation during passage through female reproductive tract

Answer 173

Although millions of spermatozoa deposited into female reproductive tract, only a few reach the site of fertilization * Most spermatozoa eliminated at selective barriers (cervix & uterotubal junction) * Majority of spermatozoa removed by phagocytosis * Damaged/immotile spermatozoa carried back to cervix by ciliated cells

Answer 174

- Maintain environment & protect spermatids from immune system through: * Blood-testis barrier * FAS-ligand (binds to FAS-receptor on T cells, triggers apoptosis of T-cells, & prevents immune attack on developing sperm) * Phagocytose residual cytoplasm

Answer 175

* Supporting testicular fluid * Substances that initiate meiosis * ABP (concentrates testosterone in close proximity to developing gametes) * Hormones affecting pituitary gland in control of spermatogenesis (e.g. inhibin)

Answer 176

Seminiferous tubules Rete testis Efferent ductules Epididymis (head, body, tail) Ductus (vas) deferens Ejaculatory duct Urethra

Answer 177

FSH = follicle stimulating hormone (gonadotropin) * LH = luteinizing hormone (gonadotropin) are released by the anterior pituitary and stimulate the leydig cells of the seminiferous tubules to secrete testosterone (LH) Stimulate Sertoli cells in the seminiferous tubules to secrete Inhibin B

Answer 178

Hypothalamus secretes GnRH GnRH tells anterior pituitary to secrete gonadotrope (LH and FSH) LH and FSH are released and target the leydig and sertoli cells of the male gonad, respectively - to secrete testosterone and inhibin b respoectfully Testosterone will travel to other target cells, resulting in development of secondary sex characteristics

Answer 179

Testosterone inhibits GnRH secretion from hypothalamus * Testosterone inhibits the anterior pituitary’s response to GnRH * Sertoli cells secrete Inhibin which inhibits the anterior pituitary’s secretion of FSH without affecting LH

Answer 180

Eunuchs (castrated servants) used to guard royal women (“less threatening”) * Castration as punishment for sex offenders (200 BC) * Impotence treated with testes extracts (700 AD) * Virility (masculine characteristics) increased using watery testes extracts (1869) * Isolation of major testicular androgen (1935)

Answer 181

Secreted by the Leydig cells, located between seminiferous tubules * Testosterone in the fetus: * Masculinizes tract & external genitalia * Testosterone during puberty & adulthood: * Growth, maturation, & maintenance of male reproductive system * Libido * Secondary sex characteristics (hair growth, voice, skin, body shape) * Bone, muscle * Brain (behaviour, cognition)

Answer 182

Mimic the effects of testosterone Excess testosterone shuts down pathway Testes stop producing sperm Testes stop producing testosterone Decreased libido & fertility

Answer 183

The first male contraceptive efficacy study using a prototype depot androgen/progestin combination demonstrates high contraceptive efficacy with satisfactory short-term safety and recovery of spermatogenesis. “Escape” when given in 6- month intervals * No escape when given in 4-month intervals

Answer 184

a largely hemodynamic event Parasympathetic nerve-induced vasodilation of arterioles through relaxation of smooth muscle * Allows blood to flow into corpus cavernosum (compresses) * Veins contract (less blood outflow) * Increased intracavernosal pressure results in erection * Neurotransmitter that mediates this is nitric oxide (NO)

Answer 185

NO - nitric oxide

Answer 186

1. NO acts on vascular smooth muscle cell, activating guanylate cyclase, which catalyzes conversion of GTP to cGMP 2. cGMP causes Ca2+ channels in vascular smooth muscle cell to close (cytoplasmic Ca2+ concentration decreases) 3. Vascular smooth muscle cell relaxes, resulting in vasodilation of penis & engorgement of erectile tissue

Answer 187

Sildenafil (Pfizer) * First tested on humans in 1991 * Was ineffective at its initial indication – angina (chest pain) * Patient recorded erections as a side effect, leading Pfizer to test the compound for erectile dysfunction * Viagra became the first drug to treat erectile dysfunction in 1998, and is still used to this day

Answer 188

Inhibits the phosphodiesterase (PDE) that catalyzes the breakdown of cGMP * This increases the availability of cGMP, promoting erection

Answer 189

- Broad ligament * Ovaries * Oviducts * Uterus * Cervix * Vagina

Answer 190

Folding of the peritoneum (mesothelium and connective tissue). Anatomy * Divided in 3 regions: 1. Mesovarium (ovaries) 2. Mesosalpinx (oviducts) 3. Mesometrium (uterus

Answer 191

Function - Supports (“hangs”) several anatomical components of the reproductive tract - Prevents friction - Houses vascular supply, lymphatics and nerves

Answer 192

Glandular organs that house the female gametes surrounded ovarian follicles. Anatomy 1. Tunica albuginea --> outer connective tissue 2. Cortex -->houses follicles and corpus luteum 3. Medulla --> houses vasculature, lymphatics and nerves

Answer 193

1. Production of oocytes (oogenesis) 2. Development of ovarian follicles (folliculogenesis) 3. Production of hormones (estradiol & progesterone)

Answer 194

Bilateral conduits between the ovaries and uterus that transport oocytes, embryos and spermatozoa (those tube things)

Answer 195

1. Infundibulum - Capture cumulus-oocyte complex - has fimbriae/finger like projections that extend and touch ovary 2. Ampulla - Site of fertilization 3. Isthmus - Transport and short-term* storage of sperm - closest to uterys

Answer 196

The ampulla of the oviducts

Answer 197

Hollow, pear-shaped muscular organ situated in the pelvic cavity. Anatomy 1. Endometrium 2. Myometrium 3. Perimetrium

Answer 198

1. Site of embryo implantation & growth 2. Sperm transportation 3. Responsive to hormones = contractions 4. Prostaglandin secretion = luteolysis

Answer 199

Muscular tunnel-like organ located at the lower, narrow end of the uterus. Anatomy 1. Endocervix 2. Ectocervix 3. Os 4. Cervical folds + crypts

Answer 200

Barrier for uterine protection - Mucus production - Non-pregnant: lubrication = facilitate sperm motility - Pregnant: mucous plug = seal pregnancy

Answer 201

Elastic, muscular canal of 7 to 10 cm in length that serves as an entrance to the female reproductive tract. Anatomy 1. Cranial region 2. Caudal region

Answer 202

- Copulatory organ (related to sexual intercourse/ copulation) - Birth canal - Mucus production for lubrication - Low pH (3.8 – 4.5) à microenvironment regulation

Answer 203

1. Provides anatomical closure to vagina 2. Minimize entry of foreign materials 3. Clitoris: highly innervated erectile tissue, homologous to penis

Answer 204

Ovarian cycle and menstrual cycle

Answer 205

Series of changes in the ovary including follicle maturation, ovulation & corpus luteum formation = folliculogenesis

Answer 206

Series of changes in hormone production & uterus structure that make pregnancy possible = uterine cycle

Answer 207

= supportive structure that secrete a variety of hormones. * Made up of multiple cell types that proliferate upon stimulation from the HPG axis. * Protect oocyte from environment, provide nutrition and biochemical support. * Contribute to oocyte maturation.

Answer 208

Folliculogenesis = follicular phase of the ovarian cycle

Answer 209

Single layer of flat cells surrounding oocytes * Represent ovarian reserve

Answer 210

Single layer of cuboidal cells surrounding oocytes * Produces estradiol (E2)

Answer 211

2 – 3 layer of cuboidal cells surrounding oocytes * Produces E2

Answer 212

- develops from secondary follicle - it grows through antral phase until its ready for ovulation Antrum: fluid filled cavity (E2) * Dependent on LH and FSH

Answer 213

- Initial corpus structure (ruptures during ovulation) * Bloody from ruptured blood vessels

Answer 214

- critical structure comprised of luteal cells - secretes P4 (progesterone) to maintain pregnancy

Answer 215

The smallest/last white thing In the absence of pregnancy, CL(corpus luteum) regresses into white small structure * Eventually disintegrates

Answer 216

1. Theca externa 2. Theca interna 3. Granulosa cells 4. Cumulus-oocyte complex

Answer 217

- Loose connective tissue - Surrounds and supports the antral follicle

Answer 218

Just beneath the theca externa of the antral follicles - LH receptors - Produce androgens (testosterone)

Answer 219

Mural granulosa cells line the inner part of the basal lamina - FSH receptors - Convert androgens into estradiol (E2) - part of antral follicles

Answer 220

LH binds LH receptors on theca interna cells of antral follicle signaling the conversion of cholesterol to testosterone testosterone enters granulosa cells FSH binds FSH receptors on granulosal cells which converts testosterone to estradiol (E2)

Answer 221

The CL is an endocrine gland formed by the remaining follicular cells after ovulation High proliferation and activity of cells. Luteal cells produce progesterone (P4)

Answer 222

Blood vessels represent ~50% of volume - Luteal cells represent ~30% - Remaining ~20% * pericytes, fibrocytes, nerves, immune and smooth muscle cells

Answer 223

cholesterol! Luteal cells have LH receptors that help this conversion

Answer 224

1. Hypothalamus secretes GnRH --> pituitary gland 2. Pituitary gland releases LH & FSH (gonadotropins) à into systemic circulation 3. LH & FSH reach the ovaries --> Ovarian follicle & CL cells have LH & FSH receptors 4. Ovaries secrete E2 (follicular phase) or P4 (luteal phase) 5. Feedback mechanisms mediate endocrine response

Answer 225

Follicle-stimulating Hormone Stimulates the growth and proliferation of granulosa cells in ovarian follicles * Stimulates production of FSH receptors on GCs - Results in increased sensitivity to FSH - Less FSH required to stimulate selected follicles * Stimulates aromatase production and increased enzymatic activity in the GCs - Converts testosterone to estradiol (E2

Answer 226

Luteinizing Hormone * Stimulates theca interna cells to produce testosterone - Testosterone diffuses into GCs * Stimulates production of LH receptors on outer GCs - Results in oocyte meiosis resumption * High concentrations after LH surge - Weakens follicle walls and collapse follicle = ovulation! - Induces formation of the corpus luteum

Answer 227

1. GnRH from hypothalamus à pituitary gland 2. LH & FSH released from pituitary gland 3. Theca cells →LH binds to theca cells →Produce testosterone 4. Granulosa cells →FSH binds GCs → ↑ recruitment of aromatase →Convert testosterone to estradiol 34

Answer 228

Estradiol (E2) is the main estrogen secreted by the follicles in the ovaries. * E2 stimulates production of FSH receptors - Increases sensitivity to FSH * E2 stimulates production of LH receptors - Establishes dominant follicle * Increased E2 production in the antral follicle induces positive feedback to the pituitary gland * Regulates ovulation

Answer 229

Increased E2 during dominant follicle stage induces an LH surge 2 days before ovulation. * LH surge changes follicle structure, weakening follicle walls and increasing antral pressure. * The follicle ruptures, releasing the cumulus-oocyte complex

Answer 230

1. Hypothalamus releases GnRH, stimulating the anterior pituitary to secrete FSH and LH 2. FSH stimulates the recruitment and proliferation of new follicles. * ↑ FSH receptors on GCs → ↑ sensitivity * ↑ aromatase activity 3. LH stimulates the follicles * Theca cells generate testosterone * Diffuses to GCs → converted by aromatase to E2 4. ↑ E2 in dominant follicle → + feedback to hypothalamus 5. Peak E2 à GnRH surge à LH surge 6. LH surge * Resumption of meiosis in oocyte * Follicle weakening and collapse = ovulation

Answer 231

LH surge converts remaining granulosa and theca cells into luteal cells = luteinization * Luteal cells generate P4 and E2 = sustains endometrium development * P4 stimulates endometrial gland secretions while E2 stimulates spiral artery development

Answer 232

No implantation = ↓ P4 & E2 --> menstruation Menstrual discharge: ~80 mL of blood, fluid, & cell debris from upper layer of the endometrium expulsed from the uterus

Answer 233

Overt menses: endometrial spiral arteries responsible for menstrual bleeding (primates) * Covert menses: endometrium is shed without bleeding due to lack of endometrial spiral arteries (other mammals) à estrus cycle 40

Answer 234

Cyclic changes in the endometrium. 1. Proliferative phase * Occurs during follicular phase * Increased E2 stimulates growth of endometrium 2. Secretory phase * Occurs during luteal phase * Increased P4 from CL stimulates development of uterine glands * Endometrium grows in thickness due to E2 & P4 3. Menstrual phase * Necrosis & sloughing of endometrium * Result of decrease in ovarian hormone secretion (E2 & P4) during late luteal phase

Answer 235

Synthetic estrogen & progesterone 1. Override the system with high concentrations of ovarian hormones 2. Negative feedback inhibition of pituitary secretions 3. No LH surge --> ovulation never occurs* * Simulate a false luteal phase 45

Answer 236

Estrogen important for cardiovascular health, bone health, & behaviour * At menopause, ovaries depleted of follicles & stop secreting estrogen (à change at ovarian level not pituitary level) * Menopause associated with increased risk of osteoporosis, hot flashes, & aging * Weak form of estrogen (estriol) made in adipose tissue * Females with more adipose tissue have higher levels of estrogen & are at less risk of osteoporosis

Answer 237

Folliculogenesis: a continuous process occurring cyclically for primordial follicle recruitment to large antral follicle formation and ovulation Oogenesis: a discontinuous process for the development of an ovum into a cell competent to further develop into an embryo when fertilized

Answer 238

* Formation and genotypic maturation of the female gametes. * Oogenesis begins during embryonic development of the female and continues throughout her reproductive lifetime. * Oocytes develop a complex cytoplasm during maturation. * Completion results in an ovum that sustains embryonic development.

Answer 239

COC = cumulus oocyte complex contains: - cortical granules - zona pellucida - corona radiata

Answer 240

cumulus oocyte complex with: cortical granules zona pellucida and corona radiata

Answer 241

Enzymes preventing polyspermy (multiple sperm fertilizing the egg)

Answer 242

- Protective membrane * Facilitates sperm binding

Answer 243

- Cumulus granulosa cells surrounding the oocyte * Intensive crosstalk with oocyte – coordinate oocyte development * Mediated by gap junctions

Answer 244

Cytoplasm provides nourishment to the embryo --> vitellus or yolk * To 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 into the uterus

Answer 245

Eccentric positioning of meiotic spindles cause unequal cytokinesis

Answer 246

1. oocytogenesis 2. ootidgenesis 3. oogenesis proper

Answer 247

Mitotic divisions resulting in more oogonia * Occurs during embryonic development Characterized by mitosis of oogonia and differentiation into primary oocytes 1. Oogonia in the differentiating ovary divide by mitosis. --> Mitotic divisions determine the size of the ovarian reserve 2. This mitosis continues until formation of primordial follicles. 3. Oogonia differentiate into primary oocytes.

Answer 248

Primary oocytes undergo meiosis I to produce a secondary oocyte & polar body. Embryonic Phase Characterized by the onset of meiosis I and nuclear arrest of primary oocytes . Adult Phase Characterized by the resumption of meiosis I, resulting in a secondary oocyte

Answer 249

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 Primordial follicle All primary oocytes are arrested in Prophase I at birth! The purpose of nuclear arrest is to protect DNA form damage

Answer 250

At the 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: * Cytoplasmic communication that crosses the zona pellucida * Critical for communication between the oocyte and granulosa cells (GC) 3. Oocytes undergo substantial growth of cytoplasm volume and cytoplasmic maturation 4. Oocytes arrested at Prophase I resume and complete meiosis I

Answer 251

Characterized by substantial growth of the cytoplasm and formation of special cellular structures. Accumulation of mRNA, proteins, substrates, & nutrients required to achieve developmental competence needed for embryonic development.

Answer 252

Meiosis I resumes after the LH surge High LH concentration stimulates LH receptors on mural GCs Deterioration of gap junctions - Reduction of oocyte cAMP - deactivation of kinases - activation of MPF

Answer 253

. Crossing-over Segments of one chromosome crossing-over to a homologous chromosome - Results in a random assortment of DNA segments between chromatids - Ensures genetic diversity in daughter cells 2. Completion of meiosis I - Asymmetric cytoplasmic division - Extrusion of 1 st polar body

Answer 254

Characterized by the continuation of meiosis II and nuclear arrest of secondary oocytes Ovulation = arrested at the metaphase II stage

Answer 255

Ovulation: arrested at the metaphase II stage nuclear arrest of secondary oocytes

Answer 256

Secondary Oocyte – DNA Arrested in Meiosis II Resumption of Meiosis II and its completion occurs only after fertilization!

Answer 257

Non-motile, infertile spermatozoa passively transported to epididymis for spermiation * Duration: 4-12 days * Upon ejaculation, spermatozoa in seminal fluid pass through ductus deferens and mix with secretions 1. Secretions from the seminal vesicles (fructose & prostaglandins) 2. Prostate gland (citric acid, acid phosphatase, zinc, & magnesium ions)

Answer 258

Ejaculated sperm is deposited in the female reproductive tract Uterus: horse, dog, pig, rat Cervix: pig, cat Vagina: cow, sheep, cat, bunny and human

Answer 259

1. Sperm deposited in upper vagina (rapid elevation of pH) 2. Passage through cervix (fast & slow phases) 3. Passage through uterus/uterine horns 4. Entry into oviducts 5. Passage up oviducts by flagellar movement & contractions of oviducts

Answer 260

During copulation, seminal fluid is deposited in upper vagina* * Seminal fluid protects spermatozoa from acidity of upper vagina * pH goes from 4.3 to 7.2 in 10 seconds * Buffering effect only lasts a few mins which is enough for sperm to approach the cervix at a pH ~6-6.5 (optimal for sperm motility)

Answer 261

1. Major barrier to spermatozoa * Cervical cells secrete mucous * Viscous and gelatinous à inhabitable and hostile to sperm * Cervical rings and folds physically inhibit sperm travel 2. Sperm reservoir * Cervical folds and crypts * Sperm get trapped in crypts * Process facilitated by cervical mucus * More spermatozoa in cervical reservoir = more sperm reaching oviduct

Answer 262

excreted by the cervix Viscous --> prevents sperm motility

Answer 263

Watery --> facilitates sperm motility (secreted in cervix)

Answer 264

Rapid transport (LIKE WATER SLIDE) 1. Spermatozoa penetrate sialomucin 2. Quickly transported through cervical canal * Aided by muscular contractions of the female tract 3. Reach the uterus Slow transport Slow transport 1. Spermatozoa swim through cervical mucus (2-3 mm/hr) 2. Sequential release of stored sperm - Slow release ensures continued availability of spermatozoa to enter oviduct for fertilization - Can last up to 3-4 days after ejaculation

Answer 265

Spermatozoa are drawn to chemoattractant secreted by COC and ovary * Contractile activity of the myometrium (uterine smooth muscle) support movement towards oviducts * Spermatozoa enters the utero-tubal junction

Answer 266

Structural changes in the sperm cells that occur in the female reproductive tract that prime sperm for fertilization Defined as alteration of glycoprotein surface of spermatozoa under influence of female tissue secretions within the reproductive tract that enables zona pellucida penetration - surface contains glycoproteins and then coated with seminal plasma and then when go through the female tract they are capacitated

Answer 267

So there are these cilia that grow on the endothelial cells of the oviducts which facilitate binding and yeah they grow with estrogen

Answer 268

sperms enter the oviduct and then they get bound to the cilia that have grown and the calcium is reduced when progesterone increases at ovulation, they release

Answer 269

Progesterone binds and causes Ca2+ channels to open

Answer 270

1. Immediate Transport *retrograde loss *phagocytosis *entrance into cervix/uterus 2. Cervix *“privileged” pathways *removal of non-motile sperm *removal of some abnormalities 3. Uterus *capacitation initiated *phagocytosis 4. Oviduct *capacitation completed *hyperactive motility 5. Fertilization *acrosome reaction *spermatozoon penetrates oocyte *male and female pronuclei form

Answer 271

Dominant follicle ruptures, releasing the cumulus-oocyte-complex (COC) * Fimbria of the infundibulum capture the COC * Once in the oviduct, the ciliated epithelium guides it deeper towards the ampulla.

Answer 272

1) arrival of the sperm 2) acrosome reaction 3) penetration of the zona pellucida 4) membrane fusion 5) fusion of the nuclei

Answer 273

When sperm reach the COC in the ampulla, they remove the cumulus cells. mediated by: 1. hyaluronidase and 2. sperm motility

Answer 274

Mediated by : 1. Hyaluronidase * On surface of capacitated sperm * Hydrolytic enzyme * Disintegrate cumulus cells 2. Sperm motility * Physically disrupts cloud

Answer 275

- Capacitated sperm can bind to ZP proteins * ZP proteins only allow species-specific binding * ZP proteins prevent any other spermatozoa to enter ovum after fertilization * Binding to ZP triggers the acrosome reaction

Answer 276

1. Fusion of the spermatozoa plasma membrane & outer acrosomal membrane 2. Pores release acrosomal enzymes (acrosin + hyaluronidase) that digest the zona pellucida 3. Inner acrosomal membrane and fusion proteins become exposed In more detail: 1. sperm makes contact with egg 2. acrosome reacts with zona pellucida 3. acrosome reacts with perivitelline space 4. plasma membranes of sperm and egg fuse 5. sperm nucleus enters egg 6. cortical granules fuse with egg plasma membrane, which renders the vitelline layer impenetrable to sperm

Answer 277

* After sperm completely penetrates zona pellucida and reaches perivitelline space, cortical granules migrate to the periphery of oocyte * Oocyte plasma membrane fuses with the equatorial segment * Immediate membrane depolarization and the fertilizing sperm is engulfed * Cortical granules are released into the perivitelline space * Sperm nuclear membrane disappears and the nucleus decondenses

Answer 278

Fast block prevention of polyspermy * Rapid depolarization of the vitelline membrane * Triggered by influx of Na+ ions from NaK+ pumps * Results in electrical barrier to sperm entry electrocutes sperm

Answer 279

Slow block prevention of polyspermy Released enzymes: * Peroxidases Harden glycoproteins to form impenetrable layer * Glycosaminoglycans Attract water into the perivitelline space - Fertilization envelope * Proteases Destroy sperm binding sites - Prevents other sperm from binding to ZP proteins

Answer 280

After fertilization: enzymes are released to prevent polyspermy - peroxidases (harden glycoproteins to form inpenetrable layer) - glycosaminoglycans: attract water into the perivitelline space (fertilization envelope) - proteases: destroy sperm binding sites - prevents other sperm from binding

Answer 281

Upon the sperm's binding, theres an ejection of PLC from the sperm head, that causes the hydrolysis of PIP by PLC to DAG and stimulates IP3 which causes Ca2+ release from ER and egg activation and cell cycle resumption Calcium oscillations allow DNA synthesis to begin and cause cell cycle to resume

Answer 282

* NAD+ Kinase activation → membrane biosynthesis * Degradation of cyclin → inactivation of MAP kinase → restoration of meiotic cell division * Stimulation of protein synthesis DNA replication, cytoplasmic maturation Ca 2+ wave triggers the completion of meiosis * Extrusion 2nd polar body * Formation of maternal pronucleus

Answer 283

1. Completion of meiosis results in a female pronucleus. 2. Sperm nucleus decondenses to form male pronucleus. 3. Sperm centriole forms microtubules that integrate with ovum microtubules, drawing the pronuclei closer. 4. Fusion of the two pronuclei: a) Cellular membranes break b) Chromatin from both intermix before condensing into chromosomes c) Embryonic development begins

Answer 284

Inability to conceive after one year of regular unprotected intercourse Caused by a myriad of endogenous and exogenous factors * Hormones, reproductive tract development, homeostasis * Epigenetics and genetics * Damage related to disease conditions, ex.: cancer and its treatment

Answer 285

* Conditions affecting spermatogenesis * Conditions affecting sperm quantity * Conditions affecting sperm quality * Environmental factors (40% of infertility cases)

Answer 286

Female infertility * Ovulation disorders * Conditions of the uterus * Fallopian tube damage or blockage * Endometriosis (50% of infertility)

Answer 287

Artificial insemination (AI) * Also called intra-uterine insemination (IUI) * Sperm is washed & then injected into uterus In-vitro fertilization (IVF) * Oocytes are harvested & fertilized in a lab * Embryo transferred into carrier or surrogate

Answer 288

Classic IVF * In-vitro Maturation: oocyte maturation (FSH, LH, E2) * In-vitro Fertilization: incubate with sperm (18h) * In-vitro Cell Culture: incubate until hatched blastocyst Intracytoplasmic Sperm Injection (ICSI) * Treatment for severe male factor sterility * Sperm quality (motility and morphology) assessed * Sperm injected into secondary oocyte cytoplasm

Answer 289

After fertilization, the ciliated epithelium of the oviduct moves the embryo towards the uterus. * Mammalian cleavage occurs every 12-24 hours. * End goal: implantation of the embryo via burrowing into the uterine endometrium

Answer 290

mammals - rotational, asynchronous cleavage fertilized egg 2-cell stage 4 cell stage 8 cell stage morula blastocyst Initial divisions of zygote to form early embryo * Involves rapid mitotic divisions with no growth phases * Results in identical daughter cells called blastomeres * Blastomeres become smaller with each division * Blastomeres up to 8-cell stage are totipotent

Answer 291

the identical daughter cells that result from the initial divisions of cells after fertilization they become smaller with each division and up to the 8-cell stage they are totipotent

Answer 292

At the 8-cell stage: * Blastomeres tightly adhere, forming the 16-cell morula * Embryo is more compact & cells lose individual identity * Mediated by calcium-activated cell adhesion molecules * E-cadherin – a cell adhesion protein present during early embryonic development * Epithin – associates with E-cadherin

Answer 293

Mediated by calcium-activated cell adhesion molecules * E-cadherin – a cell adhesion protein present during early embryonic development * Epithin – associates with E-cadherin

Answer 294

Inner cell mass * Embryoblast * Gap junctions form * Becomes the embryo proper Outer cell mass * Trophoblast * Tight junctions form * Becomes fetal placental contribution * Forms other extraembryonic membranes

Answer 295

* Occurs prior to implantation * Embryo breaks through zona pellucida due to proteases secreted by blastocyst * Inability to hatch is one cause of infertility * Altered zona pellucida * Absence of proteases * Embryos lacking zona pellucida protein leading to premature hatching

Answer 296

Apposition and Adherence: * Embryonic pole adjacent to the uterine endometrium * Adherence via cell adhesion molecules * LIF involvement, L-selectin, trophinin Penetration: * Syncytiotrophoblast, differentiated multinucleated trophoblast cells * Invasive: secrete digestive enzymes, works its way into uterine tissue * Establishes contact with maternal blood vessels Decidual reaction: * Uterine tissue responds to invasion by setting up immunological barrier (the decidua) * Becomes the maternal portion of placenta

Answer 297

Embryonic Disc Bilaminar disc: * Epiblast = maternal portion * Hypoblast = embryonic portion By week 3, the embryonic portion (hypoblast) will undergo another series of changes to form the 3 embryonic germ layers during gastrulation: 1. Ectoderm 2. Mesoderm 3. Endoderm

Answer 298

Highly complex and conserved developmental process forming internal organs and systems. 1. Ectoderm * Integumentary System (Epidermis) * Nervous System 2. Mesoderm * Circulatory System * Integumentary System (Dermis) * Musculoskeletal System * Urogenital System 3. Endoderm * Digestive System * Glandular Tissues * Respiratory System

Answer 299

Part of gastrula that develops into: - Integumentary System (Epidermis) * Nervous System

Answer 300

Part of gastrula that develops into: * Circulatory System * Integumentary System (Dermis) * Musculoskeletal System * Urogenital System

Answer 301

Part of gastrula that develops into: - Digestive System * Glandular Tissues * Respiratory System

Answer 302

Chondrion Amnion Yolk sac allantois

Answer 303

- fetal portion of the placenta - provides fetal oxygen and nourishment

Answer 304

an extraembryonic membrane - encloses the embryo - filled with amnionic fluid - provides physical protection from impact

Answer 305

initial site of blood cell production (hematopoiesis) - synthesiszes a variety of proteins - PGCs (primordial germ cells)

Answer 306

Functions in independent waste storage and respiration (non-mammals)

Answer 307

- germinal period - embryonic period - fetal period

Answer 308

first stage of prenatal development - fertilization until implantation (o-2weeks) - zygote until embryonic disc

Answer 309

second stage of prenatal development - gastrulation until the 8th week of pregnancy - neurulation - organogenesis

Answer 310

last stage of prenatal development - week 9 - birth age of viability = 22 to 28 weeks (when the baby will survive as a premie)

Answer 311

Elevated levels of estrogens (E2) and progesterone (P4) are necessary for maintaining pregnancy

Answer 312

Corpus luteum synthesizes Progesterone (P4) to keep the endometrium intact Progesterone (P4), estrogen (E2), inhibin: feedback suppression to pituitary

Answer 313

- Syncytiotrophoblast cells synthesize human chorionic gonadotropin (hCG) * Maintains the CL until gestational week 5-6

Answer 314

Both the maternal and fetal contributions of the placenta participate in hormone synthesis: * hCG* * Estriol (E3) - uterine myometrium regulation - oxytocin receptors, developments breast ducts * Progesterone (P4) - suppresses uterine contractions, cervical plug, milk glands * PTHrP (parathyroid hormone-related peptide) - mobilizes mother’s bone calcium * CRH (corticotropin-releasing hormone) - fetal lung maturation

Answer 315

Powerful contractions of the myometrium in the uterus are needed to expel the fetus in a sequence of events called labor

Answer 316

1. Oxytocin 2. Prostaglandins

Answer 317

* Polypeptide hormone * Produced in hypothalamus, released by posterior pituitary * Produced in uterus - trust hormone - important for milk release - important for uterine contractions during labor

Answer 318

* Cyclic fatty acids with paracrine functions * Produced by uterine glands * PGF 2⍺ & PGE 2 - important for uterine contractions during labour and parturition

Answer 319

= childbirth 1. Fetal hypothalamus à CRH (corticotropin releasing hormone) 2. Fetal anterior pituitary à ACTH (adrenocorticotropic hormone) 3. Fetal adrenal gland à dehydroepiandrosterone sulfate (DHEAS) and cortisol 4. Activate 3 pathways I. Positive Feedback II. Uterine Sensitivity III. Maternal Hypothalamic-Pituitary-Oxytocin Pathway

Answer 320

1. Fetal hypothalamus -CRH (corticotropin releasing hormone) 2. Fetal anterior pituitary - ACTH (adrenocorticotropic hormone) 3. Fetal adrenal gland - Fetal cortisol 4. Placenta - CRH, producing a positive feedback loop. Accumulation of CRH * Most important determinant of primate parturition * Stimulates maturation of fetal lungs + surfactant production

Answer 321

the most important determinant of primate parturition aka childbirth is the accumulation of CRH - stimulates maturation of fetal lungs and surfactant production

Answer 322

Fetal adrenal gland releases DHEAS during labor In the placenta: 1. DHEAS is converted into estriol (E3)

Answer 323

In the placenta: 1. DHEAS is converted into estriol (E3) 2. Prostaglandins and oxytocin produced 3. Stimulate changes in maternal myometrium: a) More oxytocin receptors b) More prostaglandin receptors c) More gap junctions

Answer 324

a) More oxytocin receptors b) More prostaglandin receptors c) More gap junctions

Answer 325

Oxytocin and prostaglandin F2⍺ stimulate Ca2+ channels in plasma membrane for muscle contraction Gap junctions help coordinate and synchronize uterine contractions

Answer 326

1. Maternal hypothalamus produces oxytocin 2. Released from posterior pituitary 3. Oxytocin binds to myometrium 4. Stimulate Ca2+ opening = muscle contraction 5. Cervical stretch - positive feedback

Answer 327

- Oxytocin maintains myometrium muscle tone * Reduces hemorrhaging from uterine arteries * Promotes uterus involution (size reduction) 1kg at birth to 60g post-partum

Answer 328

1. epiblast: maternal portion 2. hypoblast: embryonic portion - (ectoderm, mesoderm and endoderm)