Implantation , embryology_and_placental_development


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Implantation , embryology_and_placental_development

  1. 1. Implantation , Embryology and placental development
  2. 2. Scope• The ovarian – endometrial cycle• The decidua• Implantation• Placenta formation• Fetal membrane development
  3. 3. The Ovarian Cycle• Follicular phase • 2 million oocytes at birth • 400,000 follicles at the onset of puberty • Remaining follicles are depleted at a rate of approximately 1000 follicles per month until age 35 • Only 400 follicles are normally released during female reproductive life
  4. 4. Follicular or preovulatory phase• GnRH (Hypothalamus)  FSH(pituitary)• FSH Granulosa cells  secrete Estradiol• LH  Theca cells  secret Androgen (which are converted to Estradiol )
  5. 5. Two-Cell-Two-Gronadotropin
  6. 6. Ovulation• Estradiol ↑  LH surge• LH surge 10-12 hr  ovulation : causes the oocyte to be released from the follicle .• The ruptured follicle then becomes the corpus luteum , which secrets progest erone.
  7. 7. Luteal phase• The corpus luteum secrets progesterone for only about 11 days in the absence of hCG.• Progesterone  preparation endometrium for implantation –Highly vascularized –glandular secretions
  8. 8. The decidua• Decidualization : transformation of secretory endometrium to decidua• Depend on estrogen, progesterone and factors secreted by the implanting blastocyst.
  9. 9. Decidual Structure• Decidua : 3 parts1. Decidua Basalis2. Decidua Capsularis3. Decidua ParietalisDecidua Vera = D. Capsulais + D. Parietalis
  10. 10. •Decidual parietalis + decidual basalis like the secretory endometrium compose of 3 layers - zona compacta functional zone - zona spongiosa - zona basalis New endometrium after delivery
  11. 11. Decidual reaction• The decidual reaction is completed only with blastocyst implantation.• Predecidual changes – midluteal phase – in endometrial stromal cells adjacent to the spiral arteries and arterioles.
  12. 12. Blood supply of the decidua• The decidua capsularis is lost as the embryo-fetus grows• The decidual parietalis  spiral artery ,remain : smooth muscle, endothelium responsive to vasoactive agent• The decidual basalis  spiral artery
  13. 13. Decidual histology• NK are present in the decidua early in pregnancy• Play an important role in trophoblast invasion and vasculogenesis
  14. 14. Nitabuch layer• Zone of fibriniod degeneration in which invading trophoblasts meet the decidua• Prevent excessively deep conceptus implantation (placenta accreta)
  15. 15. Decidual prolactin• Souce of prolactin• Gene that encodes for anterior pituitary• Prolactin levels – in amniotic fluid are extraordinarily high and may reach 10,000 ng/mL – in maternal serum 150-200 ng/mL – Fetal serum 350 ng/mL (The protein preferentially enters amnionic fluid, and little enters maternal blood)
  16. 16. Roles of Decidual prolactin• Not clear1.Transmembrane solute and water transport, maintenance of amnionic fluid volum e2.Regulation of immunological functions during pregnancy – Prolactin receptors in bone marrow-derived immune cells, – Prolactin may stimulate T cells in an autocrine or paracrine manner1.Regulation of angiogenesis during implantation2.Repressing expression of genes detrimental to pregnancy maintenance : i
  17. 17. Regulation of decidual prolactin • Most agents known to inhibit or stimulate pituitary prolactin • Secretionincluding dopamine, dopamine agonists, and • do not alter decidual prolactin  TRH
  18. 18. Implantation & Formation of the Placenta & Fetal membrane• Fertilization & Implantation• Biology of the Trophoblast• Embryonic development after implantation• Organization of the placenta• Chorionic villi• Placental development
  19. 19. • Placenta = Pulmonary,Hepatic, Renal• Hemochorial type of placenta• Fetal-Maternal blood not mixed
  20. 20. Ovum Fertilization and zygote Cleavage• Ovulation : secondary oocyte Peritoneal cavity oviduct Cilia and tubal peritalsis Fertilization often takes place in ampulla
  21. 21. Fertilization•Sperm penetrates zona pellucida of secondary oocyte, trigger meiosis II.•Cortical granule reaction is a propagated response at the site of sperm entry, and is a basis for the block to polyspermy.•Secondary oocyte  Meiosis II  mature oocyte
  22. 22. • In fallopian tube : 3 days1st day : Fertilization Zygote : diploid cell2nd day : 2 cell zygote blastomere thick zona pellucida3rd day : Morular 16 cells
  23. 23. • In uterine cavity4th-5th day Morular = 16 cells Accumulate fluid - between cells Early blastocyst ( 58 cells = 5+53 )
  24. 24.           Zygot e Complete meiosis II Morula – 16 cells Blastocyst • Inner cell mass • Trophoblast Blastocyst is released from the zona pellucida IL -1α,IL -1β , hCG: endometrial receptivity
  25. 25. Implantation1. Apposition : most common occurs on the upperposterior uterine wall2. Adhesion : Integrins3. Invasion : Trophoblast• Implantation occurs 6th or 7th day after fertilization• Postovulatory production of estrogen & progesterone by corpus luteum• 20th -24th day of ovarian-endometrial cycle
  26. 26. Trophoblast differentiation• The formation of the human placenta : trophectoderm• Syncytiotrophoblast : outer multinuclear• Cytotrophoblast : inner mononucear
  27. 27. Trophoblast differentiation• After implantation is completed, trophoblast differentiates in 2 pathways – Villous trophoblast : chorionic villi – Extravillous trophoblast : decidua , myometrium and maternal vasculature
  28. 28. 12 th day after fertilizationChorionic villi• Primary villi : cytotrophoblast core• Secondary villi : mesenchymal core• Tertiary villi : angiogenesisVilli which failure of angiogenesis >> HydatidiformmoleAnchoring villi• cytrophoblast cells columns• anchore to the decidua at basal plate
  29. 29. Embryonic Development after Implantation• 9 th day : Implantation : Blastocysts Blastocyst wall : uterine cavity  single layer with flattened cells Blastocyst wall : Inner wall  Thicker wall, 2 zones 1. Trophoblasts 2. Inner cell mass : embryo-forming• 10 th day : Blastocyst totally encase within the endometrium
  30. 30. Embryonic Development after Implantation• 7½ days after fertilization : inner cell mass or embryonic disc >> ectoderm -mesode rm - endoderm• Enclosing space between embryonic disc and trophoblast : amniotic cavity• Cells within amniotic cavity condense to form the body stalk >> Umbilical cord
  31. 31. Placental development• Modification of the maternal vasculature by trophoblast, occur in the first half• Important in preeclampsia and IUGR• Extravillous trophoblast• Interstitial trophoblast• Endovascular trophoblast• Villous trophobast and and anchoring cytotrophoblast
  32. 32. • Interstitial trophoblast s - penetrate the decidua a nd myometrium - preparation o f vss for endovascular trophoblasts• Endovascul ar
  33. 33. The chorion• The chorion is composed of cytotrophoblasts and fetal mesodermal mesenchyme that survives in a relatively low-oxygen atmosphere.• Chorion frondosum : the area of villi in contact with the decidua basalis, fetal compone nt of the placenta• the chorion laeve : contact with the decidual capsularis .A portion of the chorion becomes the avascular fetal membrane that abuts the de cidua parietalis
  34. 34. Maternal Regulation of Trophoblast Invasion and Vascular Growth• Decidual natural killer cells (dNK) – attract and promote invasion of trophoblast into the decidua and promote vascular growth – IL-8 and INF-inducible protein-10, VEGF and placental growth factor (PlGF)• The extravillous trophoblast: invasion of endometrium and spiral arteries• urokinase-type plasminogen activator: plasminogen plasmin
  35. 35. • Trophoblasts are further secured by fetal fibronectin• Trophoblast glue• presence of fFN in cervical or vaginal fluid is used as a prognostic indicator for preter m labor
  36. 36. 1. Decidua capsularis2. Uterine wall3. Uterine cavity4. Placenta5. Decidua parietalis6. Decidua basalis7. Chorion leave8. Embryo9. Connecting stalk10. Yolk sac11. Chorion frondosum12. Amnion13. Chorionic cavity14. Amniotic cavity
  37. 37. Uteroplacental vasculatureBefore 12 weeks post fertlizationInvasion and modification of the spiral a. up to theborder of the deciduas and myometrium12-16 weeks post fertlizationInvasion of the intramyometrium segments ofspiral a.Remodeling : Dilated , low resistanceuteroplacental vesselsSignificance in the pathogenesis of preeclampsia and IUGR
  38. 38. Maternal blood flow• 1 month after conception, maternal blood enters the intervillous space in “ fou ntain-like bursts “ from the spiral arterie s.• Blood is propelled outside of the maternal vessels and sweeps over and directly bath es the syncytiotrophoblast.• Villous branching : Chorion frondosum >> Cotyledon :single a and v.
  39. 39. Placental growth and maturation• 1st trimester Placental growth more rapid than fetal growth• GA 17 wk by LMP placental weight = fetal weight• At term placental weight = 1/6 of fetal weight
  40. 40. At termDiameter 185 mmVolume 497 mlThickness 23 mmWeight 508 gCotyledon : 10-38lobes (fibrous septa;incomplete partition)
  41. 41. Placental maturationAt term• Thin layer of syncytium• Villi : thin wall capillary• Significant reduction of cytotrophoblasts• Decreased stroma• Increased number of capillary
  42. 42. Hofbauer cell• Fetal macrophage• Round, vesicular, eccentric nuclei• Very granular or vacuolated cytoplasm• Increase in numbers & maturation state out throughout pregnancy• Phagocytic , immunosuppressive phenotype• Produce a variety of cytokines• Paracrine regulation of trophoblast functions
  43. 43. Changes in placental architecture that can cause decreased efficiency of placental exchange• Thickening of basal lamina of trophoblast or capillaries,• Obliteration of certain fetal vessels• Fibrin deposition on the villi surface
  44. 44. Fetal circulation 2 umbillical artery (deoxygenated blood) placenta : chorionic vessels : capillary network in villi Oxygenated blood 1 umbillical vessels
  45. 45. Fetal circulation•chorionic plate - chorionic vessels - responsive to vasoactive agents•Truncal artery - perforating branch through chorionic plate - supply one cotyledon•End diastolic flow within umbilical artery appears at GA 10 wk.
  46. 46. Maternal circulation Basal plate Intervillous space Venous orifice in basal plate Uterine vein
  47. 47. Maternal circulation(1) Leave maternal circulation(2) Flow into an amorphous space lined bysyncytiotrophoblast, rather than capillary endothelium(3) Return through maternal veins withoutproducing arteriovenous-like shunts that would prevent maternal blood fromremaining in contact with villi long enough for adequate exchange
  48. 48. • Spiral arteries : perpendicular to the uteine wall• Spiral veins : parallel to the uterine wall• This arrangement aids closure of veins during a uterine contraction and prevents entry of maternal blo od from the intervillous spacePrincipal factors regulating blood flow inthe intervillous space•Arterial blood pressure•Intrauterine pressure•The pattern of uterine contractions•Factors that act specifically on arterial walls.
  49. 49. Breaks in placental barrier• Maternal leukocytes and platelets• D- antigen isoimmunization• Erythroblastosis fetalis• Fetal cells : Lymphocytes , CD 34+ mesenchymal stem cells• Microchimerism : Maternal autoimmune disorders ; Lymphocytic thyroiditis , sclero derma , SLE
  50. 50. Immunological Considerations of the Fetal–Maternal Interface• Lack of uterine transplantation immunity• Survival of the conceptus in the uterus – Decidual natural killer cells with their inefficient cytotoxic abilities – Decidual stromal cells – Invasive trophoblasts• Placenta : immunologically inert• Villous trophoblast : absent MHC antigen(I,II)• Invasive cytotrophoblast : MHC Class I
  51. 51. • Trophoblast HLA (MHC) Class I Expression – Short arm of Chromosome 6• Uterine Natural Killer Cells (uNK)Permit and limit trophoblast invasion• HLA-G Expression in Trophoblastonly in extravillous cytotrophoblastsin the decidua basalis and in the chorion laeve Embryos used for IVF do not implantif they do not express this soluble HLA-G isoform
  52. 52. Amnion• the inner most fetal membrane• provide almost all of the tensile strength of the fetal membrane• Collagen + fibrous like mesenchymal cell• avascular• Lack nerve, lymphatics, smooth muscle 7th or 8th day of embryonic development : Small sac cover dorsal surface of the embryo >> engulf embryo>>adhere to chorion leave
  53. 53. Structure of Amnion• The inner – single layer of cuboidal epithelium – embryonic ectoderm• the outer – A row of fibroblast-like mesenchymal cells – Embryonic disc mesoderm • A few fetal macrophages in the amnion • Lacks smooth muscle cells, nerves, lymphatics, and importantly, blood vessels
  54. 54. Amnion Epithelial CellsProduce• PGE2 >> initiation of labor• fetal fibronectin• tissue inhibitor of metalloproteinase-1• brain natriuretic peptide• CRH• vasoactive peptideMesenchymal Cell•Fibroblast layer•Synthesis of - interstitial collagens (majority of tensile strength) - cytokine : IL-6, IL-8, MCP-1
  55. 55. Metabolic Function• contain amniotic fluid• solute & water transport (maintain AF homeostasis)• produce bioactive compoundsAMNIOTIC FLUIDIncrease : until GA 34 weeksAt term : 1000 mL
  56. 56. Umbilical cord• Dorsal surface growths faster than ventral surface• Yolk sac & Allantois is incorporated to form gut yolk sac: smaller pedicle: longer• Middle of 3rd month : amnion fuse with chorion laeve• Body stalk -> umbilical cord or funis
  57. 57. At term•Cord : 2 arteries, 1 vein•Rt umbilical v. dissappears early during development•Arteries are smaller than veinMeckel diverticulum : umbilical vesicle remnant, : from umbilicus to intestineThe most common vascular anomaly : absence of 1 umbilical artery
  58. 58. Umbilical cord• Diameter 0.8 - 2 cm• Length 30 -100 cm (Average 55 cm)• Abnormal short cord < 30 cm• Tortious vss which are longer than cord create nodulation -> false knot• Spiral vss in cord, prevent clamping
  59. 59. •Wharton jelly - extracellular metrix - a specialized connective tissue - increases in volume at parturition to assist closure of pla cental blood vss