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Zona Pellucida (from previous lecture)
- a specialized extracellular matrix surrounding the developing oocyte
- lies outside the oocyte but under the cumulus oophorus & subsequent granulosa cells
- contains the ZP3 glycoproteins
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The 1st 17 Days After Fertilization: Key Features
- after fertilization, the zygote is still in the fallopian tube; it will start dividing rapidly, rolls down the fallopian tube, & make it’s way to the uterus
- goes through several EQUAL divisions for the 1st 3 days
- the first 3 divisions (2 → 4 → 8 cells) are synchronous & produce 8 IDENTICAL cells called blastomeres
- day 1: 2-cell embryo (1st embryonic cleavage)
- day 2: 4-cell embryo (2nd embryonic cleavage)
- day 2.5-3: 8 cell embryo (embryo biopsy stage)
- after/around day 3: ASYNCHRONOUS divisions, called the Morula
- cells are no long the same size or shape & they can no longer all become an embryo
- some cells will go on to become the embryo, others will differentiate into supporting structures (eg. amnion, placenta)
- the Morula (days 3-4) is STILL IN THE fallopian tube
- Morula morphs into → the Blastocyst, which is in the fallopian tube up until ~day 5
- ~ day 6 the Blastocyst will get to the uterus
- in order to implant, it has to shed the Zona Pellucida (called Zonal Hatching)
- Blastocyst exists from days 4-14 (implantation)
- Gastrula exists from days 15-17 (3 germ layers)
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Blastomere
- a cell that could become a completely new embryo on its own
- result of the 3 synchronous divisions that the zygote undergoes in the first 1-3 days after fertilization
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Blastocyst
- purpose is to create the hypoblast & the epiblast (bilaminar disc), 2 kinds of cells that will go on to become the embryo
- in addition, it creates the nutrient source for the embryo
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Gastrulation
- occurs after the blastocyst period (days 15-17)
- this is when the 3 germ layers are formed (endoderm, mesoderm, ectoderm)
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The 1st 3 Divisions
- the zygote, still inside the Zona Pellucida, undergoes synchronous mitotic divisions while moving down the fallopian tube
- the Zona Pellucida is what PREVENTS the zygote from adhering to the walls of the fallopian tube (ZP prevents ectopic pregnancy)
- the 1st cleavage to form the first 2 blastomeres occurs on day 1 (24-30 hours) after fertilization
- by day 2.5 - 3 (48-60 hours) 8 blastomeres have formed without ANY ↑ in zygote size because of the Zona Pellucia
- this is called COMPACTION: every time there’s a cell division the cells have to be half the size they were
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What proteins are responsible for compaction?
- cadherins
- are drawn to each other, draw the cells close
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Morula (“Mullberry”)
- formed at/after the 8-cell stage when cell divisions become asynchronous to establish the Inner Cell Mass (ICM, becomes the embryo) & Trophoblast (becomes the placenta)
- early cleavages that form the Morula still occur in the fallopian tube
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What structure from the Morula is the source of embryonic stem cells (ES cells)?
the ICM, because it will go on to give rise to the embryo
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What determines the seriousness of a genetic defect?
- the time during development that it occurs
- the EARLIER a chromosomal (or other) abnormality occurs, the more SERIOUS it’s going to be
- “when an abnormality occurs later → individuals are mosaics”; they generally have less severe phenotypes than those with complete non-disjunction, deletion, or translocation events
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Preimplantation Genetic Diagnosis (PGD)
- blastomeres can be biopsied (removed) & tested for genetic disorders - the remaining blastomeres still form a normal embryo & placenta
- embryo biopsies nowadays are blastocyst (4 cell stage) biopsies
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Blastocyst Formation
- day 4: the Morula has arrived in the uterus
- further cleavage of the Morula → Blastocyst
- blastocoel cavity filled with fluid forms
- the blastocyst sheds the Zona Pellucida as it expands in size because of fluid filling the blastocoel (Blastocyst Hatching)
- no overall size increase is possible unless the embryo sheds the zona pellucida
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On what day does the Blastocyst attach to the uterine endometrium?
day 6
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Mid-Implantation (Day 8-12)
embryo develops into Bilaminar Disc consisting of the epiblast & hypoblast
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End of Implantation (12-14)
hCG is produced by the syncitiotrophoblast into the maternal circulation, ensuring the survival of the Corpus Luteum & its continued production of progesterone
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Why doesn’t the mother immunologically reject an embryo or fetus that it would otherwise see as a “foreign body”?
- Decidual Cells (endometrial stromal cells) produce PGE2 (Prostaglandin E2) at the start of blastocyst implantation
- PGE2 blocks activation of both T-cells & Natural Killer (NK) cells
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Other Roles of PGE2 (Prostaglandin E2)
- PGE2 is instrumental in the contraction of thecal cells (~ smooth muscle cells) responsible for expelling the oocyte during ovulation
- PGE2 production is critical for stimulating contraction of uterine myometrial smooth muscle cells during labor
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What gives rise to all 3 germ layers?
- the EPIBLAST, which is part of the bilaminar disc
- NONE come from the hypoblast (which basically just deaminates to allow endoderm formation)
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ICM (Morula) → epiblast & hypoblast (Blastocyst)
- epiblast gives rise to all 3 embryonic germ layers
- Trophoblast (Morula) gives rise to placenta & most extra-embryonic tissues
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What is the overall Spontaneous Abortion (Miscarriage) rate?
- 50%
- most studied SAB embryos were grossly abnormal
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What are the major causes of early (1st trimester) spontaneous abortions?
- 1. Chromosomal Abnormalities
- 2. Cleavage Problems (incorrect mitosis)
- 3. Progesterone Insufficiency
- (if a woman has 2 SABs she will be preventatively put on progesterone replacement for her 3rd pregnancy)
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What is the silver lining of spontaneous abortions?
early losses of pregnancy keep the rate of congenital malformations at birth to 2-3%
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