16 - Gametes Fertilization and Implantation

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  1. 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
  2. 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
  3. 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
  4. 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
  5. What are the products of male meiosis?
    Forms a total of 4 spermatids with symmetric cytokinesis
  6. 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
  7. 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
  8. 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
  9. 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
  10. 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
  11. 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
  12. What diseases are associated with increased paternal age?
    • Achondroplasia
    • Marfan syndrome
    • Multiple endocrine neoplasia (MEN)
    • Autism spectrum disorders
    • Schizophrenia
  13. 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
  14. 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
  15. 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
  16. How does the cortical reaction
    • 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
  17. 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
  18. What is the secondary block to polyspermy?
    Rapid but temporary depolarization of the egg membrane upon sperm fusion
  19. 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
  20. 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
  21. What are the outermost cells of the blastocyst and what do they become?
    Trophoblast cells; these will become the fetal chorion, or placenta
  22. 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
  23. 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
  24. 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
  25. 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
  26. 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
  27. 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
  28. What occurs after the trophoblast binds to the
    • 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
  29. 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)
  30. 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
  31. 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
  32. 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
  33. What symptoms signal an ectopic pregnancy?
    • Slow rise in hCG
    • Vaginal bleeding (sometimes)
    • Severe abdominal pain
    • Missed menstrual period(s)
  34. 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
  35. 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
  36. 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
  37. 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
  38. 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
  39. 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)
  40. 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
  41. What will form out of the connecting stalk?
    The umbilical cord vessels will form from the connecting stalk
  42. 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
  43. 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)
  44. 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)
  45. 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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16 - Gametes Fertilization and Implantation
Gametes, Fertilization, and Implantation
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