Fertilization Flashcards
Specialized histone that wraps DNA with disulfide bonds and keeps the chromatin condensed in the head of the sperm cell.
Protamine
Part of the sperm cell covered in sheath and contains the mitochondria to power the cell.
Mid-piece
Part of the sperm cell that contains axial filament with 9+2 array of microtubules, an end-piece, and dynein regulation.
Tail
Sperm capacitation
1) Sperm display increased frequency and amplitude of the flagellar beat of the tail/ decrease in progressive movement
2) Capacitated sperm are able to bind to the zone pellucida, surrounding the egg
Acrosome reaction
The outer membrane of the acrosome region fuses with plasma membrane of the sperm. This leads to the release of hyaluronidase and acrosin via a calcium-sensitive G-protein channel; hyaluronidase digests cumulus layer (corona radiata) and acrosin digests zona pellucida and oocyte membrane.
Sperm binding is mediated by ____ on the zona pellucida
Glycoprotein ZP3
Anatomical site of acrosome reaction
Ampulla of the fallopian tube (site of fertilization)
Fertilin
Sperm protein responsible for sperm-oocyte fusion
Zona Reaction
Exocytosis of cortical granules and formation of the ZP3-F glycoprotein so that other sperm can no longer bind, preventing polyspermy.
Oocyte activation
Reawakening of oocyte through 2nd meiotic division;
Identified morphologically through exocytosis of cortical granules
Extrusion of 2nd polar body
Semen Analysis Components
Volume, Concentration, Motility, Morphology, Viscosity, Rate of progression
Normal viscosity on Semen Analysis
Normal
Normal volume on Semen Analysis
> 2 mL
Normal motility on Semen Analysis
> 50%
Normal morphology on Semen Analysis
14% normal (one tail, etc.)
Normal rate of progression on Semen Analysis
> 50% grade 3 or 4
Window of opportunity for uterine implantation
Day 20-24 of menstrual cycle
Pinopodes
Small finger-like projections on the apical surface of the endometrial epithelium; promoted by progesterone and prevented by estrogen; makes uterus more receptive to implantation; involved in endocytosis of macromolecules and uterine fluid
Normal sperm concentration on semen analysis
20 million/mL
Implantation occurs _____ after fertilization
6-7 days (BlastoCYST STICKS at day 6)
Decidualization
The thickening, vascularization, glandular growth, and differentiation of the endometrium into decidua—the thick uterine lining of modified mucous membrane that is critical for trophoblast invasion and formation of the placenta; induced by progesterone and cAMP; begins before implantation, but enhanced by interaction with embryonic trophoblast.
Small finger-like projections on the apical surface of the endometrial epithelium; promoted by progesterone and prevented by estrogen; makes uterus more receptive to implantation; involved in endocytosis of macromolecules and uterine fluid
Pinopodes
What specific changes can be seen during decidualization?
1) Accumulation of glycogen and lipids
2) Change in the nature of the extracellular matrix
3) Prolactin and IGFBP-1 production
4) Activation of COX-2 -> increases synthesis of PGE2
5) Recruitment of dNK cells into decidua
* process enhanced when interaction with embryonic trophoblast occurs
What are trophoblasts?
The outer layer of the blastocyst, which make contact with the uterus following blastocyst hatching and form the placenta.
When does blastocyst hatching occur?
Day 5 after fertilization
What is blastocyst hatching?
The blastocyst escapes from the zona pellucida; required for implantation; unfertilized eggs do not hatch
What is the blastocoele?
Within the blastocyst, polarized epithelium pumps water and ions into the center, forming the blastocoele. It will be the primary yolk sac, then obliterated as extra embryonic structures form.
IGFBP-1
Insulin-like growth factor binding protein-1; protein that binds IGF-1, which is secreted by liver via Growth Hormone stimulation; produced along with prolactin in decidualization.
dNK cells
Human decidual Natural Killer cells, or uterine lymphocytes; recruited to uterus upon decidualization
Decidualization is dependent on _______
progesterone and cAMP
Decidualization begins during ______
the secretory (luteal) phase of the menstrual cycle BEFORE an embryo is present, and only continues if enhanced by interaction with an embryonic trophoblast.
When is the uterus receptive to trophoblast attachment and invasion?
Day 20-24 of the menstrual cycle
What characterizes a receptive uterus?
1) Active secretion of peptides and glycoproteins into the uterine lumen
2) Decreased proliferation due to decreased estrogen secretion
3) Pinopodes - small finger-like projections; formation dependent on progesterone
Roles of hCG
1) Maintain corpus luteum for progesterone production, until week 8, when placenta makes enough progesterone
2) Immunosuppressive: apoptosis of endometrial T-cells
3) Growth-promoting: cytotrophoblast differentiation into syncytiotrophoblasts
4) Critical for implantation: controls trophoblastic invasiveness; produced by blastocyst on day 18
5) Decreases myometrial contractility early in pregnancy
6) Stimulates testosterone production from fetal leydig cells
7) Stimulates relaxin: increases GFR and RBF
Promotes cytotrophoblast differentiation into syncytiotrophoblasts
hCG
What is the half-life of hCG
It is highly glycosylated, giving a long half-life of 24-36 hours
Decidua basalis
Decidual tissue under the implanting embryo
Decidua capsularis
Decidual tissue that overlies the embryo
Decidua parietalis
Decidual tissue covering the remainder of the uterine surface
Decidua
The thick layer of modified mucous membrane that lines the uterus during pregnancy and is shed with the afterbirth
Stage 1 of Implantation: Apposition
Unstable initial connection between trophoectoderm and endometrial lining. The microvilli of the trophoblast interdigitate with uterine pinopodes.
Stage 2 of Implantation: Adhesion
A stronger interaction created by ligand-receptor interactions, which lead to cytoskeletal changes in epithelial cells that dislodge them and allow access of the trophoblast to the basal lamina.
Stage 3 of Implantation: Invasion
Decidualization become pronounced and closure of the luminal epithelium occurs so that the developing blastocyst is totally implanted within the uterine wall.
Where does implantation usually occur?
In the upper, posterior wall of the midsagittal plane; but can occur anywhere within the cavity.
Placenta previa
When the placenta covers the opening in the mother’s cervix.
• Typically occurs when implantation takes place near the cervix
• Requires C-section delivery
Placenta accreta
When the placenta attaches abnormally to the myometrium (muscular layer of the uterine wall), usually due to implantation over the site of a prior uterine scar (such as from prior C-section or removal of uterine fibroids)
Ectopic pregnancy
A pregnancy that develops outside the uterine cavity; incidence is 1 in 50-250 pregnancies (0.4-2.0%); fallopian tube is most common ectopic site of implantation; carries high risk of rupture and hemorrhage
Common ectopic sites
Tubal
Abdominal
Ovarian
Cervical
What are syncytiotrophoblasts?
They form from trophoblastic cells during invasion; extend long protrusions and secrete TNF-alpha; process is important in interfering with the expression of e-cadherin and beta-catenin, assisting in the dislodgment of epithelial cells.
Complete Mole
1) Diandric diploid: 46XX or XY
2) One or two sperm fertilize an anucleate egg
3) . “SNOWSTORM”: cystically dilated spaces without fetal parts
4) NO FETAL DEVELOPMENT
5) Malignant potential: choriocarcinoma or gestational trophoblastic neoplasm
6) Elevated hCG, large uterus, hyperemesis, vaginal bleeding, early preeclampsia, hyperthyroidism
7) Placental overgrowth
Partial mole
1) Diandric triploid: 69 XXY
2) FETAL PARTS (with syndactyly)
3) p57 expressed in partial mole yet not in complete mole
Treatment for HER2+ CA
Trastuzumab or Herceptin
BRCA 1 and 2 are autosomal ______
dominant
Dinoprostone
PGE2 gel which stimulates cervical effacement
Misoprostol
Oral PG1 analog which causes uterine contractions
Mifepristone/ Misprostol
1) Abortifacent: can be used up 9 weeks
2) Competitive progesterone receptor antagonist
3) Leads to decimal breakdown, detachment of the blastocyst, and further decrease in progesterone secretion
4) Followed by misoprostol (PGE-1 analog)
SIde effects of ED drugs
HA Facial flushing Dyspepsia Nasal congestion Dizziness
DDI with ED drugs
Nitrate vasodilators
Alpha-adrenergic blockers
CYP450 inhibitors
Sildenafil side-effects
Photosensitivity
Blurred vision
Loss of blue-green color discrimination
Tadalafil side effects (Cialis)
Back and muscle pain
Tadalafil
PDE-5 inhibitor; Vasodilator; treats ED, BPH, and PAH (pulmonary arterial HTN)
Drugs that cause gynecomastia
Some Hormones Create Awesome Knockers: Spironolactone Hormones Cimetidine Alcohol Ketoconazole
Corpus luteum
Hormone-secreting empty ovarian follicle that develops following the release of an ovum (ovulation) with each menstrual cycle; maintained by hCG produced by the trophoblast cells of the blastocyst; main source of progesterone and estradiol production for the first 8-10 weeks of pregnancy
What maintains the corpus luteum?
The hCG produced from trophoblast cells of the blastocyst for the first 8-10 weeks of pregnancy
LH-like hormone that maintains corpus luteum following LH surge
hCG
Noncellular porous layer of glycoproteins secreted by the oocyte 6-7 days after fertilization
Zona Pellucida
Active secretion of peptides and glycoproteins into the uterine lumen occurs during _____ of menstrual cycle
Days 20-24; the window of uterine receptivity
The part of the blastocyst that invades the uterine wall during implantation
Inner cell mass
Trophoblasts surrounding implanted blastocyst differentiate into:
cytotrophoblasts and syncytiotrophoblasts
Form a syncytial multinucleate cell environment that eventually forms the villi of the placenta, where nutrient and oxygen transfer occurs; do not express MHC antigens (expression could trigger immune rejection)
Syncytiotrophoblasts
Cells that invade deep into the uterine lining to anchor the pregnancy and form the placental attachments to the uterus; express unusual (immunosuppressive) HLA antigens
Cytotrophoblasts
The extent of ____ corresponds with the degree of invasiveness of trophoblasts.
decidualization of the uterus
_____ expressed by the extravillous trophoblast downregulate T-cell and NK cell activation in the local environment of the placenta
HLA-G molecules
Embryo first begins producing hCG in the ____ stage
morula
Time point at which hCG first becomes detectable in the mother’s serum
- Implantation
- 3 weeks after the last period (days 20-24 of menstrual cycle)
- 6-7 days after fertilization: blastoCYST STICKS at day 6
Heterotopic pregnancy
a rare situation when there is an intra-uterine and extra-uterine pregnancy occurring simultaneously; ectopic embryo is difficult to treat due to risk of harming the viable intrauterine pregnancy (i.e. with methotrexate or surgery)
Time point at which hCG first becomes detectable in mother’s urine
4-5 weeks after last period: aound the time of the first missed period
At what value of the serum pregnancy test can an intrauterine pregnancy be ruled out in favor of an ectopic pregnancy?
1500 (discriminatory zone), or 2000 to be safe; intrauterine pregnancy must be absent on ultrasound
When does the maternal and fetal circulation first come into contact?
2 weeks post-fertilization (primary chorionic villi formation)
____, which are shaped via fusion of invading syncytiotrophoblasts, fill with maternal blood that chorionic villi are bathed in.
Lacunae
Villi with fully formed capillary structures in the middle; form at about 3 weeks post-fertilization
Tertiary villi
O2 needs to cross a single _____ layer to diffuse into the fetal circulation.
syncytiotrophoblast
Villi covered with syncytiotrophoblasts
Floating villi (site of nutrient and waste exchange)
Villi covered with cytotrophoblasts
Anchoring villi
In the process of _____, cytotrophoblasts invade and surround _____, replacing their endothelial lining and lowering their resistance to increase blood flow to the placenta.
- endovascular invasion
* uterine spiral arteries
In the process of _____, cytotrophoblasts invade the entire endometrium and the first third of the _____.
- interstitial invasion
* myometrium
Trophoblast cells are stained with _____
cytokeratin
