L06: Fertilisation Flashcards by Gayathri Sethunath

Q

How does cumulus-oocyte complex enter + move along uterine tubes?

A

Follicular fluid contains chemoattractants that attract fimbrae to ovulation site
Muscular contractions of tube transports it through

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Q

Describe the journey of sperm through female tract in terms of numbers

A

~4-250 million sperm ejaculated
100,000 make it into uterus
1000 enter each tube via uterotubal junction
10-100 sperm actually reach egg

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Q

Describe the journey of sperm through the female tract

A

Seminal plasma is alkaline so buffers acidic vagina, PSA from prostate causes clotting of semen to prevent flowback
Other enzymes cause liquefaction after 1hr
Sperm must get through cervical mucus to enter uterus - least viscous around ovulation
Contractions of myometrium propel sperm towards tubes
Stem enters tube through uterotubal junction
Chemotaxis (maybe P4) attracts more sperm towards tube with egg in
Muscular actions of tube move sperm towards egg

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Q

Where in the female tract does fertilisation commonly occur?

A

Ampulla

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Q

What changes occur during ovulation that make it easier for sperm to get to egg?

A

Thinning of cervical mucus (day 9-26), effect of oestrogen
Contraction frequency of myometrium increases
Chemotaxis towards correct tube

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Q

What are the obstacles faced by sperm in female tract?

A

Uterine cavity is v small
Has to squeeze through muscular walls
Folded lumen of uterine tubes cause sperm to get stuck
Viscous fluid within tubes

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Q

What is the window of fertilisation determined by?

A

Spermatogenesis viable for 5 days, egg only for 24h

Hence fertilisation can occur in ~6 days

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Q

How does sperm interact with egg?

A

Penetration of cumulus
Binding to ZP + acrosome reaction
Penetration of ZP and fusion to egg

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Q

How does sperm penetrate cumulus cells?

A

Cumulus cells embedded in hyaluronic acid matrix (holds cells together)
Sperm has hyaluronidase enzyme that breaks down + disperses cumulus

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Q

How does sperm penetrate ZP + fuse w egg

A

Hyper motility of sperm allows it to get through ZP after acrosome reaction
Sperm enters perivitelline space + equatorial segment of sperm head fuses w egg
Interaction if izumo protein + juno receptor
Egg plasma membrane engulfs sperm into vesicle
Causes large influx of Ca2+ from site of sperm entry

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Q

What occurs after sperm fuses w egg?

A

Influx of Ca2+ ACTIVATES oocyte

PLC zeta then leads to Ca oscillations every 3-15 mins for several hrs

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Q

What does activation of egg lead to?

A

Release of meiotic block

2. block to polyspermy

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Q

How does block to polyspermy occur?

A

Ca influx —> depolarisation which inhibits further fusion
Cortical granules release protease —> zona reaction
- hardening of ZP preventing penetration
- cleavage of ZP2 (key for sperm binding)
Junk receptor lost from egg

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Q

What occurs once sperm in inside egg?

A

Sperm DNA decondenses
Make + female pronuclei move towards eachother, guided by sperm aster (forms from centriole)
Formation of spindles from centrosome

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Q

What is syngamy?

A

Male + female genetic material combine 
Pro nuclear membranes break down 
Chromatic intermixes 
New nuclear envelope forms 
End of fertilisation + start of embryogenesis = end of syngamy + beginning of cleavage

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Q

What day does implantation occur?

A

Day 6/7

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Q

What day does zygote usually enter uterus

A

Day 4, aided by relaxed musculature due to progesterone

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Q

What is a major instance zygote has to cross to enter uterus?

A

Isthmic sphincter of uterotubal junction - this is relaxed by progesterone

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Q

What occurs during cleavage?

A

Zygote divides until morula stage (16 cells), no formation of cytoplasm hence overall size stays the same, each cell gets smaller

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Q

What is the significant about the 8 cell stage of cleavage?

A

embryo transfer most commonly occurs for IVF (embryonic genome is activated)
genetic testing can be done pre implantation (PCR/FISH)

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Q

When does the embryonic genome get activated?

A

4-8 cells stage

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Q

What controls development before activation of embryonic genes?

A

Egg cytoplasm - hence egg quality + maturation v important
Poor cytoplasm —> problems w early development
Embryo growth stimulated by autocrine + paracrine GFs (from tubes)

Q

When does blastocyst form? Describe this process

A

Day 5
Formation of trophoblast + ICM
Formation of fluid filled cavity (blastocoele)
Formation of polarity (embryonic + anembryonic)

Q

How does the blastocoele form?

A

During late morula stage, fluid absorption occurs
Na/K pump of morula cells pump Na into cavity causing water to follow
Tight junctions between trophoblast cells keeps liquid within cavity

What is the role of trophoblast cells?

Produces hCG which maintains corpus luteum until placenta formation

When is embryo transfer done in IVF?

Usually 8 cell stage But if difficult to tell which embryo is best, can be done at blastocyst stage as key development stages have been completed hence embryos more likely to implant - activation if genome - past stage of totipotency (first differentiation occurred)

When does the embryo hatch out of ZP?

Day 6 onwards,just prior to implantation | Blastocyst expands out of hole in ZP, anembryonic pole first

How does implantation occur?

Window around 4 days Pinapodes form on endometrium that absorb uterine fluid drawing blastocyst to endometrium Immobilises blastocyst

What can increase risk of dizygotic twins?

Maternal age Fertility treatment - more eggs ovulated Multiple embryo transfer

What can increase risk of monozygotic twins?

IVF - embryo may be slightly damaged, increasing risk of splitting

Risk of monochorionic + monoamniotic twins?

Monochorionic - twin-twin transfer syndrome | Monoamniotic - entanglement of umbilical cord

What are the layers of the endometrium? What are the cell types found?

Upper functional layer - proliferates + sheds Basal layer - where functional layer is rebuilt from Stromatolites cells & luminal epithelial cells

Risk of monochorionic + monoamniotic twins?

Monochorionic - twin-twin transfer syndrome | Monoamniotic - entanglement of umbilical cord

What are the layers of the endometrium? What are the cell types found?

Upper functional layer - proliferates + sheds Basal layer - where functional layer is rebuilt from Stromatolites cells & luminal epithelial cells

Risk of monochorionic + monoamniotic twins?

Monochorionic - twin-twin transfer syndrome | Monoamniotic - entanglement of umbilical cord

What are the layers of the endometrium? What are the cell types found?

Upper functional layer - proliferates + sheds Basal layer - where functional layer is rebuilt from Stromatolites cells & luminal epithelial cells

Risk of monochorionic + monoamniotic twins?

Monochorionic - twin-twin transfer syndrome | Monoamniotic - entanglement of umbilical cord

What are the layers of the endometrium? What are the cell types found?

Upper functional layer - proliferates + sheds Basal layer - where functional layer is rebuilt from Stromatolites cells & luminal epithelial cells

Risk of monochorionic + monoamniotic twins?

Monochorionic - twin-twin transfer syndrome | Monoamniotic - entanglement of umbilical cord

What are the layers of the endometrium? What are the cell types found?

Upper functional layer - proliferates + sheds Basal layer - where functional layer is rebuilt from Stromatolites cells & luminal epithelial cells

Risk of monochorionic + monoamniotic twins?

Monochorionic - twin-twin transfer syndrome | Monoamniotic - entanglement of umbilical cord

What are the layers of the endometrium? What are the cell types found?

Upper functional layer - proliferates + sheds Basal layer - where functional layer is rebuilt from Stromatolites cells & luminal epithelial cells

Risk of monochorionic + monoamniotic twins?

Monochorionic - twin-twin transfer syndrome | Monoamniotic - entanglement of umbilical cord

What are the layers of the endometrium? What are the cell types found?

Upper functional layer - proliferates + sheds Basal layer - where functional layer is rebuilt from Stromatolites cells & luminal epithelial cells

Risk of monochorionic + monoamniotic twins?

Monochorionic - twin-twin transfer syndrome | Monoamniotic - entanglement of umbilical cord

What are the layers of the endometrium? What are the cell types found?

Upper functional layer - proliferates + sheds Basal layer - where functional layer is rebuilt from Stromatolites cells & luminal epithelial cells

Risk of monochorionic + monoamniotic twins?

Monochorionic - twin-twin transfer syndrome | Monoamniotic - entanglement of umbilical cord

What are the layers of the endometrium? What are the cell types found?

Upper functional layer - proliferates + sheds Basal layer - where functional layer is rebuilt from Stromatolites cells & luminal epithelial cells

Risk of monochorionic + monoamniotic twins?

Monochorionic - twin-twin transfer syndrome | Monoamniotic - entanglement of umbilical cord

What are the layers of the endometrium? What are the cell types found?

Upper functional layer - proliferates + sheds Basal layer - where functional layer is rebuilt from Stromal cells + luminal epithelial cells

What happens to the endometrium during proliferative/follicular phase?

Functional layer proliferates due to oestrogen Proliferation of stromal cells + stromal oedema Epithelial layers form glandular prtrusions into stroma - stromal cells secrete nutritional substances into these glands

What happens to the endometrium during secretory/luteal phase?

Stromal cells secrete nutritional substances into glands for embryo development prior to placenta Development of spiral arteries ready for implantation

what happens if no implantation occurs?

No hCG to maintian corpus luteum hence it breaks down + P4 conc falls Spiral arteries are hormone sensitive - lack of P4 --> collapse + necrosis, lost in menses

Ectopic pregnancy

1 in 100 pregnancies, 90% in uterine tubes Can rupture BVs + uterine tube Risk factos: history of PID, tubal surgery, IUD coil, failed sterilisation