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What happens during metaphase?
- Each duplicated chromosome lines up separately on the metaphase plate
- Microtubule spindles on each side of this plate attach to centromeres of all duplicated chromosomes in metaphase
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What happens during Meiosis I?
- The csomes pair and synapsis/crossing
- over occurs, and homologous DNA is exchanged
- The linked csomes line up on the metaphase plate, w/ each centromere attached only to one spindle pole
- The pair of duplicated csomes split, and one duplicated csome moves to each spindle pole
- NOTE: there is no splitting of the centromere or separation of sister chromatids
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What happens during Meiosis II?
- There is no S phase
- The 23 duplicated csomes align on the metaphase plate
- The sister chromatids split
- 23 single csomes move to each spindle pole
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When does male meiosis occur?
- Begins at puberty
- There is a continuous supply of stem cells (spermatogonia) that give rise to committed primary spermatocytes that initiate meiosis
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What are the products of male meiosis?
Forms a total of 4 spermatids with symmetric cytokinesis
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When does female meiosis occur?
- Meiosis I begins by 5th month of fetal life
- Arrests at synapsis of meiosis I until around time of ovulation
- Oocyte arrests in metaphase of meiosis II
- Fertilization triggers completion of meiosis II
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What is asymmetric division?
Meiosis I results in one large secondary oocyte, but leaves 2 or 3 polar bodies that are unsuitable for fertilization and are discarded
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Why do women show substantially higher rates of nondisjunction than men?
- Vulnerable to problems with synapsis
- Premature resolution of chiasmata leads to maternal and paternal homologues aligning separately on the metaphase plate
- Premature separation of sister
- chromatids contributes to errors in distribution of chromosomes during
- meiosis
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Why do sex csome aneuploidies occur at about the same rate in gametes from men or women?
- Nondisjunction of the X and Y chromosomes occurs at a high rate compared to that of autosomes in male meiosis I because of the limited region of homology that supports synapsis of X and Y
- To contrast: 80% of autosomal aneuplodies occur in eggs rather than sperm
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How does the spindle assembly play a role in aeuploidies?
- The spindle assembly “tensional” checkpoint functions poorly in meiosis, especially female meiosis
- Meaning anaphase is allowed to begin even if all chromosomes are not properly aligned on the metaphase plate with equal tension exerted on centromeres by spindle fibers
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How does increased paternal age affect the integrity of the sperm’s DNA sequence?
- Point mutations accumulate
- Leads to dominant phenotype disorders
- However, there is no increased aneuoploidy
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What diseases are associated with increased paternal age?
- Achondroplasia
- Marfan syndrome
- Multiple endocrine neoplasia (MEN)
- Autism spectrum disorders
- Schizophrenia
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What are the key features of sperm that are important for fertilization and early development?
- Acrosome – digestive enzymes used to bore through zona pellucida
- Nucleus – tightly condensed
- Mitochondrial Sheath – provides energy to drive flagellum
- Flagellum - microtubule motor‐based structure that drives swimming movement of the sperm
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What is sperm capacitation?
- Biochemical and functional changes in sperm that occur upon exposure to the female reproductive tract
- This includes exposing receptors for binding corona radiate and zona pellucida
- Also induces rapid motility
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What are the key features of the oocyte that are important for fertilization and early development?
- Zona pellucida – important for sperm recognition/binding; triggers acrosome rxn
- Cortical Reaction – blocks polyspermy
- upon sperm-egg fusion
- Barrier to premature-ectopic implantation within oviduct
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How does the cortical reaction
occur?
- When sperm fuses, there is a release of cross-linking enzymes from the cortical granules
- This causes rapid cross- linking and impermeability of the zona pellucida to further sperm entry
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What happens when the acrosome
reaction occurs?
- The acrosome allows sperm to penetrate zona pellucida
- Sperm and egg cell membranes fuse
- Sperm enters egg, resulting in degradation of sperm mitochondria and tail
- Sperm nucleus decondenses and becomes male pronucleus
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What is the secondary block to polyspermy?
Rapid but temporary depolarization of the egg membrane upon sperm fusion
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What major events occur in the egg immediately following fertilization?
- Fusion of sperm and egg membranes also triggers release from metaphase arrest and completion of meiosis II
- Egg nucleus decondenses and is now called the female pronucleus
- Fusion of pronuclei forms zygote
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What events take place in the zygote before implantation?
- In the early stages, the cells undergo mitotic division without G0
- After about three days the zygote is a cluster of cells (morula)
- Compaction occurs; cell-cell adhesions called adherens junctions form between many of the cells, especially the outermost layer in the ball of cells
- Fluid secretes into morula forming blastocyst cavity (blastocyst)
- Blastocyst hatches from zona pellucida through release of proteolytic enzymes at 5-6 days of development
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What are the outermost cells of the blastocyst and what do they become?
Trophoblast cells; these will become the fetal chorion, or placenta
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What will the inner cell mass become?
- This ball of cell in the blastocyst at the embryonic pole will subdivide into the epiblast and the hypoblast
- The epiblast will mainly form the embryo proper and amniotic sac
- The hypoblastvwill become the yolk sac
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What are dichorionic, diamniotic twins?
- These occur when the zygote splits within the first few cleavage divisions leading to the formation of two blastocysts in the zona pellucida
- These zygotes will implant separately
- Do not share a chorion or amnion
- Occurs in ~25% of twins
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What are monochorionic, diamniotic twins?
- Occurs when there is a complete splitting of the inner cell mass
- These will implant as one unit and share a
- placenta/chorion
- Will have separate amniotic sacs
- Occurs in ~75% of twins
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What is twin-twin transfusion syndrome?
- Unequal placental circulation leads to one twin
- being better nourished than the other
- Growth disparity that may require early delivery
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What is the first step of normal implantation?
- Binding of trophoblast to uterine endometrium
- Most commonly occurs at the posterior position
- within the main body of the uterus
- Usually occurs within main body or fundus
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What is placenta previa?
- This is when implantation occurs close to the cervix but within the uterus and the placenta grows over the cervix and prevents safe vaginal delivery
- Can result in hemorrhage and death of mother and baby
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What occurs after the trophoblast binds to the
endometrium?
- The endometrium triggers proliferation of the trophoblast
- A single layer of cells outside the trophoblast, but inside the synctiotrophoblast, forms; known as cytotrophoblast
- The invasive syncytiotrophoblast forms
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What does the syncytiotrophoblast do?
- Secretes enzymes (e.g., matrix metalloproteinases) that degrade the uterine wall
- Actively pulls blastocyst into wall of the uterus adhesion and forward migration of the syncytial cell leading edge
- Secretes human chorionic gonadotropin (hCG)
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hGC
- Human chorionic gonadotropin
- Endocrine hormone essential for maintenance of pregnancy
- Can be detected in the urine as early as 1 week following the start of implantation
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How does the endometrium respond to trophoblast invasion?
- The endometrium changes the epithelioid character of its cells with the accumulation of glycogen and lipids; these cells engulf the trophoblast to nourish the embryo
- Signals angiogenesis (blood vessel formation)
- Signals endometrial gland secretion
- Growth factors and cytokines are released
- All of the above is geared towards nourishing the embryo and formation of the placenta
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Why are ectopic implantations problematic?
- 1-2% of pregnancies
- The surfaces where the egg implants don’t have room for the fetus to develop, and the tissues, while responding with angiogenesis, are not able to form stable vascular networks
- Results in rupture of fallopian tube (if this is where implantation occurs) and hemorrhage from unstable vessels
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What symptoms signal an ectopic pregnancy?
- Slow rise in hCG
- Vaginal bleeding (sometimes)
- Severe abdominal pain
- Missed menstrual period(s)
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What are the known risk factors for ectopic pregnancy?
- Smoking – impairs motility of oviduct smooth muscle and of cilia on oviduct epithelial cells
- Pelvic inflammatory disease – scarring and mechanical blockage of the oviduct
- Maternal age > 24 – reason unknown
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Bilaminar embryonic disk
- Formed from the inner cell mass in day 7-8
- Consists of hypoblast (consisting of small cuboidal cells; transient tissue contributing to yolk sac lining) and the epiblast (consisting of columnar epithelium; closest to embryonic pole and trophoblast)
- The hypoblast and epiblast are separated by a basement membrane
- The bilaminar embryonic disk has a very simple oval shape and simple structure at this stage
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What structures will the epiblast contribute to later in development?
- During gastrulation, the epiblast will
- contribute to the definitive ectoderm, mesoderm, and definitive endoderm
- The epiblast will also be the source of primordial germ cells and extraembryonic mesoderm
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What is the amniotic cavity/sac?
- This cavity is formed within the inner cell mass
- Fluid secretion separates a single layer of amnioblasts (which form the amniotic membrane) from the epiblast cells, forming the amniotic cavity
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What is the amnion?
- Formed by the amniotic cavity and amniotic membrane
- This will eventually circle the embryo and provide a shock buffer against injuries
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What is the extraembryonic mesoderm?
- Formed around day 9
- Cells migrate out from the epiblast to lie between the trophoblast and the interior structures of the implanting conceptus (yolk sac/embryonic disk/amnion)
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What will the extraembryonic mesoderm differentiate into?
- Forms a connective tissue where cells lie within a reticular matrix
- Differentiates into connective tissue and blood vessels of the chorion
- It will form the blood vessels of the definitive yolk sac and of the connecting stalk that joins the posterior end of the embryonic disk and amnion to the chorion
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What will form out of the connecting stalk?
The umbilical cord vessels will form from the connecting stalk
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What will happen to the extraembryonic mesoderm as the chorion grows?
As the chorion grows much faster than the yolk sac/embryonic disk/amnion, the extraembryonic mesoderm splits so that it lines the inside of the trophoblast and the outside of the yolk sac/embryonic disk/amnion with a cavity (chorionic cavity) in between
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What is the status of the chorion at the end of the second week of development?
- The syncytiotrophoblast, cytotrophoblast, and extraembryonic mesoderm are now all part of the chorion
- The chorion entirely and equally surrounds the chorionic cavity (derived from the former blastocyst cavity)
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What is primitive uteroplacental circulation?
- First the syncytiotrophoblast forms lacunar spaces (through fusion of intracellular vesicles into tubes which connect to the extracellular space)
- Once the lacunae are forms, they fill with maternal blood and glandular
- secretions; this occurs as the syncytiotrophoblast invades the uterine tissue
- This process of blood filling the lacunae is called primitive uteroplacental circulation
- This is how the early embryo gets its nutrients and oxygen (via diffusion)
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How are primary chorionic villi formed?
- Around days 12-14 the sytotrophoblast will proliferate in local patches surrounding the chorionic cavity (this is stimulated by the extraembryonic mesoderm)
- These proliferative patches will produce extensions which will jut into the syncytiotrophoblast
- Eventually these extentions will work their way into the lacunar network
- The outgrowths are primary chorionic villi
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