Final Exam Flashcards
Conception and fertilization can be defined as the fusion of _____to form a _____.
gametes; zygote
What stages are the oogonium, primary oocyte, and secondary oocytes locked in?
Oogenium is just granulosa cells, primary is locked in prophase 1, secondary is locked in metaphase 2.
What are spermatids the result of?
Secondary spermatocytes and meiosis II
What is nondisjunction?
Improper chromosome separation during anaphase due to improper spindle attachment.
Describe Robertsonian translocation.
The whole of a chromosome is joined end-to-end with another.
Male factor infertility relates to issues with ____, ____, and ____ of sperm.
production; function; delivery
Female factor infertility relates to _______ disorders, _____ obstruction, and ________ anomalies.
ovulatory; tubal; and uterine
Endometriosis is a progressive, malignant, inflammatory, and chronic condition in which endometrial tissue develops outside the uterus (T/F).
False! It is benign not malignant.
In endometriosis, how does the invading tissue behave?
It thickens, breaks down, and bleeds as well with each cycle.
Name the three main types of endometriosis.
Peritoneal, ovarian, and deep-infiltration.
PCOS is a reproductive circulatory disorder (T/F).
False, endocrine.
There is no one accepted definition of PCOS, but what are some key characteristics?
Hyperandrogenemia, hyperandrogenism, oligoanovulation, and polycystic ovaries.
What are some coocurrences of PCOS?
Diabetes, Cardiovascular Disease, Infertility, and Mood/Eating Disorders
Which androgens are most elevated in PCOS
Testosterone (total and free) and DHEA-S produced by ovaries and adrenal gland.
How do cysts form in PCOS?
Hyperandrogenism, hyperinsulinemia, and changes to paracrine signalling alter follicle growth. So… cystic follicles.
How does PCOS affect the HPO axis?
Increased luteinizing hormone (LH) and decreased follicle stimulating hormone (FSH)
How are sperm harvested for ARF?
Sperm is collected and evaluated for count, motility, progression, volume, viscousity.
Centrifuged to separate the parts and then motile sperm are resuspended in liquid media.
How are oocytes harvested in ARF?
Ovaries are stimulated, cycle and pituitary are suppressed. Ovulation is triggered and oocytes are collected.
Intrauterine Insemination (IUI) is primarily indicated with ______ infertility, donor sperm, and altered ovulation.
male-factor
How is ICSI different from IVF?
Instead of co-culturing the oocyte and sperm, a sperm is directly injected into an egg.
What are seminiferous tubules?
Where sperm production occurs, they are kept separate from circulation by the blood-testis barrier (Sertoli cells).
What are Sertoli and Leydig cells?
Sertolis are “nurse” cells part of the seminiferous tubule that help with spermatogenesis.
Leydigs are in the tubule wall and produce testosterone once puberty happens.
Which hormones stimulate spermatogenesis?
LH and FSH, testosterone and inhibin do the negative feedback on receptors in the brain.
What is the initial diploid cell that does mitosis to form primary spermatocytes?
Spermatogonia. Meiosis gives 2 secondary spermatocytes then 4 spermatids. Differentiation creates sperm.
What is spermiation?
Breakdown of Sertoli junctions and release of sperm from seminiferous tubules, to rete testes which concentrate it, then epididymis.
Spermatogenesis takes about 90 days (T/F).
False, 70!
What is capacitation?
Process in the female repro tract wherein cholesterol and glycoproteins are removed from the sperm head. Now, it can bind to the zona pellucida of the ovum.
Rates of infertility are lower in less industrialized countries (T/F).
False, more!
How is chromatin organization different in sperm than oocytes?
Sperm DNA is tightly packed, oocytes have less methylation and more loose chromatin.
Sperm histones are mostly replaced with protamines.
How are protamines different from histones?
They wrap around DNA more tightly, but they still go through post-translational modification (phosphorylation).
How are oocytes formed in utero?
Primordial germ cells colonize the cortex of the primordial gonad and replicate to 7 mil by 20 weeks. Primary oocytes are the leftover 2 mil that survive after this. Atresia in childhood leaves 40k eggs at puberty.
What are granulosa cells and theca folliculi?
Pre-antral stage: Granulosa cells secrete glycoproteins to form zona pellucida around primary oocyte. Theca folliculi is specialized connective tissue responsive to LH.
In the antral stage of oogenesis, fluid fills space between granulosa cells to form the central ______ and _____ follicles.
antrum; secondary
Where does the first polar body come from?
Primary oocyte. It will divide into two polar bodies. The secondary oocyte will divide into one mature ovum and one more polar body.
A Graffian follicle is the mature ovum follicle (T/F).
True, the wall is weaker and contractions will release the ovum out.
What is the corpus luteum?
Formed when the follicle wall collapses, it’s the endocrine organ during pregnancy.
How does the fertilized egg get to the uterine wall?
Peristaltic movements of the fallopian tube move it to the posterior uterine wall.
What are the three key events of the sperm-egg fusion process?
Attachment: Protein-protein or protein-carbohydrate mediated.
Membrane apposition: Hinge motion draws the membranes together.
Lipid mixing: Cytoplasmic continuity.
What stops a second sperm from entering the egg?
Fast block is an instant ionization (Ca+ influx). Cortical reaction (zonal inhibiting proteins and mucopolysaccharide release by cortical granules). Impenetrable fertilization barrier, zona pellucida gets thick.
Neural tube defects occur very early in pregnancy (T/F).
True
What are the two most common neural tube defects?
Anencephaly (open brain) and Spina bifida (closure of spinal cord)
Folate is the _____ name for vitamin B9, whereas folic acid is the _______ manmade version.
generic; oxidized monoglutamate
How is folic acid absorbed?
Hydrolyzed to monoglutamate in the gut then active transport across mucosa. Dihydrofolate reductase reduces to THF.
What is the main form of folate in plasma?
5-methyl-THF
Colonic microbiota synthesize folate (T/F).
True
Name 3 functions of folate.
Purine and thymidine synthesis
Methyl donation
Homocysteine —> Methionine conversion in SAM synthesis. Important for methylation.
About 2/3 of NTD can be prevented by increasing _____ intake at the beginning of pregnancy.
folate
What are high homocysteine levels a risk factor for?
Heart disease and stroke in the mother, and maybe baby.
Folate has no role in placental development (T/F).
False!!! Basically in everything (EVT invasion, angiogenesis, MMP secretion)
What are the three folate receptors in the placenta?
Folate receptor (FOLR A and B)
Reduced folate carrier (RFC)
Proton-coupled folate transporter (PCFT)
Which folate receptor shows greater expression in pregnancies complicated with birth defects?
PCFT as an adaptive response
How does folic acid uptake differ with gestational diabetes?
Leptin and TNF-a downregulate folic acid uptake. GDM modulates uptake by placental cells by increasing PCFT expression.
Which folate receptor is implicated in IFGR?
RFC
In preterm babies, which folate receptor is less expressed?
FOLR1
Maternal folate deficiency decreases ____ signalling.
mTOR
What is placental abruption?
When placenta separates from the wall before birth. Folic acid helps prevent this.
What has low paternal folate been shown to cause?
Low placental weight, and birth defects in mice
What are some foods that interact negatively with folic acid?
Alcohol, chocolate, tea.
What are three risks of too much folate?
Cancer, allergy, and undetected B12 deficiency.
What are the roles of Choline, B12, and B6?
Choline is a source of methyl groups + needed to synthesize phospholipids
B12 is important for methionine synthase and homocysteine conversion
B6 does a lot. Protein metabolism + cognitive development.
The placenta, fetus, and amniotic fluid account for ____% of the total pregnancy weight gain.
35
What is the role of Vitamin A in pregnancy?
Sperm production, normal reproductive cycles. For fetuses, HPA and organ development. Low Vitamin A can have consequences in early childhood too.
What is xerophthalmia?
Result of vitamin A deficiency, which also can cause increased maternal/infant mortality, anemia, and slow growth.
Where is excess Vitamin A kept?
In the liver bc it’s fat-soluble. Excess can result in teratogenesis.
Vitamin D3 (cholecalciferol) is metabolized how?
To the hormonally active 1.25-dihydrocycholecalciferol. Active Vitamin D binds to intracellular receptors that function as transcription factors for calcium metabolism and bone growth.
Where can B12 be found and what does deficiency lead to?
Animal products; anemia, muscle issues, because it is needed for RBCs and angiogenesis.
What are the essential fatty acids?
ALA, converted to EPA then DHA at a limited rate. So it’s needed from food or supplements like plant oils, its later forms can be found in fish oil.
Linoleic acid
Omega-3s are involved in phospholipids esp for retina, brain, and sperm.
What are eicosanoids?
Signalling molecules that come from Omega 3s, involved in cardio, pulmonary, immune, and endocrine systems. Omega 6 ones are inflammation mediators and platelet aggregators.
Iron plays a profound role in organ development, especially the _____, as it is the most prevalent transition metal within the ____.
brain
What is zinc essential for?
Protein synthesis, cell division, and nucleic acid metabolism.
Zinc slightly reduces ________.
preterm births
Alters a number of hormones associated with labour onset, and immune function.
Where is the majority of the body’s iodine stored?
thyroid. it’s important for hormone development.
What can childhood iodine deficiency cause?
Reduced cognition
What food should iodine-deficient people avoid?
Cruciferous veggies
Vitamin E is a fat-soluble vitamin that ________.
acts as an antioxidant by targeting free radicals. Enhances immune function and prevents clots.
What is the metabolized form of Vitamin E?
a-tocopherol
Most aneuploidies are benign (T/F).
False, most are lethal, especially monosomies.
Trisomy 16 accounts for 16% of first trimester ____.
spontaneous abortions
Who is most affected by rare diseases?
Children, especially unsolved ones with no family history.
What is the role of mosaic mutations in ASD?
ASD brains were found to have deleterious somatic mutations in SOME parts of the brain, indicating a mix of genetic and somatic mutation (identical twins share autism way more than fraternal).
Paternal gamete mutations are more frequent than maternal (T/F).
True
What are selfish mutations in sperm?
Mutations that cause sperm to produce two sperm. Growth advantage proliferates the bad mutation. Can cause cancer.
BAP and ENU are two examples of _____.
nasty chemicals that cause genetic damage
What are polyaromatic hydrocarbons?
PAH comes from lots of natural (fire, plant synthesis) and anthropogenic (exhaust, unburned petrol, smoke) sources. It is carcinogenic and teratogenic and they induce minisatellite mutations that are unstable, noncoding, and small (10-100bp).
BAP is a male germ cell mutagen that broadly impacts _____.
microsatellite and tandem repeat DNA, dividing sperm are especially sensitive
How does BaP cause bp mutations?
Unable to be properly metabolized, they latch onto nucleotides rendering them unrecognizable.
What is the effect of BaP on ovaries?
Even worse than sperm, exposure induces mutations that deplete ovarian follicles in mice (oogenesis).
Carcinogens have to meet a threshold to cause significant damage (T/F).
False, one mutation can cause a chain reaction.
How many genes are imprinted in mammals?
About 1%
What are differently methylated regions?
A sequence that get imprinted. Germline acquires methylation during gametogenesis and the somatic type does after fertilization. Imprinted genes often lie in clusters.
When does imprinting occur?
Gametogenesis and early embryogenesis.
What are the effects of Prader-Willi and Angelman syndrome?
Intellectual disability, low birth weight, prolonged or poor suckling, etc.
What is the difference between Prader-Willi and Angelman syndrome?
In Prader-Willi, the non-imprinted paternal gene area is deleted, in Angelman it’s the maternal.
What does X chromosome inactivation compensate for?
The imbalance between X and Y, the X chromosome has more than 10x the number of genes.
Males upregulate their one X, and women silence one X.
When does X inactivation occur in women?
When RNA is transcribed from Xist (Tsix) gene is transcribed on one chromosome, it spreads in cis from their site of synthesis.
50-60% of genes escape silencing in humans (T/F).
False, 20-30%
Name some pros and cons of having two X chromosomes.
Improved blood pressure regulation and brain injury protection
Greater risk of autoimmunity
CRISPR is a simplified version of the bacterial ______ antiviral defense system.
CRISPR-Cas9
CRISPR makes ____________ to render specific sections of genes inactive.
double strand breaks
How does CRISPR add things to genes?
Cas9 fuses to an enzyme which mutates specific bases, which can then reverse a mutation. It can also recruit RNA polymerases, attach fluorescent proteins for visualization, etc.
Name 3 limitations of CRISPR.
Difficult to deliver material to cells in large numbers. Not 100% accurate in terms of targets and changes aren’t 100% effective as in they may not create the effect.
Endocrine disruptors mimic or interfere with the function of _________ in the human body.
hormones
Dioxins are a byproduct of _________ production and paper bleaching and fires.
herbicide
What is the difference between disruption, deformation, and dysplasia?
Disruption is breakdown of well-formed tissue, deformation is extrinsic mechanical forces on normal tissue, and dysplasia is a lack of normal organization in tissue.
What are the critical periods of action for teratogens?
Embryonic period (0-8 weeks) and fetal period. Max susceptibility is between 3-8 weeks, organogenesis.
What was thalidomide intended to treat?
Sedative for morning sickness and pregnant women in the 50s, it didn’t show effects in rodents and it looked like a genetic condition (absence of limbs/severe shortness)
What is phocoemelia?
Congenital deformity caused by thalidomide, where the hands and feet are bound to the trunk, absent or grossly underdeveloped.
The majority of thalidomide by-product function is anti-inflammotory and anti-________.
angiogenic, paracrine pathways are needed for limb bud formation. There’s also immunosuppressive activity, inhibiting TNFa release.
Once smooth muscle covers the newly formed _____, thalidomide has no effect
vessels
R(+) is the sedative form of thalidomide and S(-) is the teratogenic (T/F).
True
Release of methylmercury compounds caused ________ in fetuses near Minamata Bay in Japan.
neurological abnormalities
Methylmercury readily crosses the _______ and causes focal necrosis of ___________, leading to deficits in attention, behaviour, cognition, and motor skills. Symptoms can resemble _________, convulsions, and visual problems.
placenta; neurons and glial cells; cerebral palsy
What is the mechanism of action of mercury in the brain?
It has a strong affinity for sulfur. It will interfere with enzyme and protein synthesis by binding to sulfydryl or thiol groups.
Name some traits of fetal alcohol syndrome.
Small head and eye openings, short nose, smooth philtrum, flat midface, less active brain.
What is the method of action for alcohol as a teratogen?
May be several: premature migration of neural crest cells, genes related to cytoskeleton, cells forming the face and cranial nerves, and cell death from superoxide free radicals
Both ethanol and acetylaldehyde modify metabolism of ______________ indirectly affecting fetal growth via nutrient deprivation.
carbohydrates, proteins, and fats
Alcohol can lock neuroblasts in an undifferentiated state and increase histone transacetylase activity (T/F).
False, DNA methyltransferase
How does alcohol impact the hippocampus?
It’s the area responsible for learning and memory. Alc can destroy the cells and, during critical periods, irreversibly alter the brain’s capacity to learn and remember.
Retinoic acid (Accutane) is important for ________, heart, and jaw formation,
anterior-posterior axis
What is the mechanism of action of retinoic acid as a teratogen?
Alters HOX expression, binding to neural crest cells and inhibiting migration. RA degrading enzymes then cause a deficiency and more anomalies.
Which endogenous teratogen can be upregulated by the herbicide Glyphosate?
Retinoic Acid
How does nicotine impact fetal development?
Binds to nicotinic acetylcholine receptors in the brain, increasing levels of several neurotransmitters in various brain structures.
Cannabinoids have no real evidence of teratogenicity yet (T/F).
True
Where are the G-coupled cannabinoid receptors found in the brain?
The parts involved in emotional + behavioural reactions, homeostasis, learning, memory, and decision-making.
How does the endocannabinoid system communicate?
When the post synaptic membrane is activated, the cannabinoid is made on demand and then the THC overwhelms the system and travels backwards.
What are some common teratogenic mechanisms of prescription drugs?
Folate antagonism, neural crest disruption, endocrine disruption, oxidative stress…
ACE inhibitors in late pregnancy are associated with _____________.
renal insufficiency, toxicity, hyperkalemia, bad lungs bad face and prematurity
When is the critical period for Warfarin as a teratogen?
Central nervous system development (6-9 weeks)
Valproic acid inhibits activity of _________ causing autism-like development and structural birth defects. It blocks folate, causing _________ defects and decreases PAX1 transcription causing rib and vertebrae defects.
histone deacteylases; neural tube
CMV and Herpes are almost always fatal in late embryos (T/F).
False, early
When are babies at risk for neonatal herpes?
When the mother contracts herpes WHILE late in pregnancy. It can also be spread in the first few weeks of life from a cold sore kiss.
When is toxoplasmosis a risk to a fetus?
If it’s caught for the first time just before or during pregnancy, then there’s a 40% chance. Can cause miscarriage or stillbirth or eye/brain damage.
What is the most common sign of congenital cytomegalovirus?
Hearing loss
Diabetes is an endocrine disorder that can be caused by endocrine disruptors (T/F).
True
Which of the following is not a classic route of exposure for endocrine disruptors?
A) Ingestion
B) Absorption
C) Injection
D) Trans-placental
E) Inhalation
D
Describe the research done with indigenous communities and EDCs.
The hypothesis was people living in rural areas would have less PCB chemicals in their bodies. But actually, their breast milk was the highest ever recorded and 7x higher than Mtl control group due to their nutrient rich diet (bioaccumulation).
NOAEL stands for: No Observed ______ Effect Level.
Adverse
Phthalates (plasticizers) are typically used to make plastics ____________.
more flexible and harder to break
Which reproductive effects have phthalates demonstrated?
Spontaneous abortion, testicular atrophy, teratogenicity, specifically in male offspring.
Descended testicles have an increased likelihood of developing cancer (T/F).
False, undescended (cryptorchidism) do.
In hypospadias, the urethral opening is on the ______ of the penis.
underside
What is DES used for?
Xenoestrogen with high binding affinity; Mostly from the 40’s to 70’s to treat morning sickness in pregnant women and was associated with premature delivery.
Mothers exposed to DES often had abnormalities or cancer of the _______ in women, and abnormal testicle growth and development in men.
reproductive organs
What is the mechanism of action of DES?
Inhibits the Hoxa10 gene which participates in the patterning of reproductive systems under estrogen regulation. Knockout mice have inferitility and reproductive issues.
DES daughters have a 40x higher risk of ________, a very rare cancer of the vagina and cervix as well as risk for breast cancer.
clear cell adenocarcinoma
What was DDT used for?
Pesticide in WWII which bioaccumulates in animal fatty tissue, persistent in the environment and can travel far in the upper atmosphere.
DDT is banned across the world (T/F).
False, still used in some developing countries
How does DDT affect birds?
Especially high food chain birds exposed to fish, they get eggshell thinning. DDT inhibits calcium transport.
Atrazine is the most widely used ________ in the US and it has caused frogs to become _______ at low doses.
pesticide; intersex
How did atrazine cause hermaphroditism in frogs?
Chemical castration, reducing testosterone ten fold.
What is BPA?
Weak xenoestrogen, we are exposed through dust inhalation, thermal paper dermal, plastic ingestion, etc.
What is the mechanism of action of BPA?
Binds to estrogen receptors to cause gene changes in target organs like the brain, ovaries, uterus, mammary glands. There are diet-associated methylation changes as well.
BPA inhibits transcription of __________.
DNMTs
What are some components of the precautionary principle of public health.
take preventative action when uncertain, shift burden of proof to proponents, explore alternatives and increases public participation.
Endocrine ______ are associated with fetal growth restriction and thyroid issues.
disruptors
Glucocorticoids are hydrophilic and work on transcription (T/F).
False, lipophilic
How does estrogen upregulate the HPA axis?
Blocks negative feedback by downregulating glucocorticoid binding
Alcohol may inhibit transport of _____ across the placenta by decreasing expression of transport proteins.
folic acid
How does folic acid lower preeclampsia risk?
Reducing homocysteine and improving endothelial cell function
