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Similar to Implantation , embryology_and_placental_development
Implantation , embryology_and_placental_development
- 1. Implantation , Embryologyand placental development
- 2. Scope • The ovarian– endometrial cycle • The decidua • Implantation • Placenta formation • Fetal membrane development
- 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
- 5. Follicular or preovulatoryphase • GnRH (Hypothalamus) FSH(pituitary) • FSH Granulosa cells secrete Estradiol • LH Theca cells secret Androgen (which are converted to Estradiol )
- 6.
- 7. 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.
- 8. Luteal phase • Thecorpus luteum secrets progesterone for only about 11 days in the absence of hCG. • Progesterone preparation endometrium for implantation –Highly vascularized –glandular secretions
- 9. The decidua • Decidualization: transformation of secretory endometrium to decidua • Depend on estrogen, progesterone and factors secreted by the implanting blastocyst.
- 10. Decidual Structure • Decidua : 3 parts 1. Decidua Basalis 2. Decidua Capsularis 3. Decidua Parietalis Decidua Vera = D. Capsulais + D. Parietalis
- 11. •Decidual parietalis +decidual basalis like the secretory endometrium compose of 3 layers - zona compacta functional zone - zona spongiosa - zona basalis New endometrium after delivery
- 12. Decidual reaction • Thedecidual reaction is completed only with blastocyst implantation. • Predecidual changes – midluteal phase – in endometrial stromal cells adjacent to the spiral arteries and arterioles.
- 13. Blood supply ofthe 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
- 14. Decidual histology • NKare present in the decidua early in pregnancy • Play an important role in trophoblast invasion and vasculogenesis
- 15. Nitabuch layer • Zoneof fibriniod degeneration in which invading trophoblasts meet the decidua • Prevent excessively deep conceptus implantation (placenta accreta)
- 16. Decidual prolactin • Souceof 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)
- 17. Roles of Decidualprolactin • Not clear 1.Transmembrane solute and water transport, maintenance of amnionic fluid volum e 2.Regulation of immunological functions during pregnancy – Prolactin receptors in bone marrow-derived immune cells, – Prolactin may stimulate T cells in an autocrine or paracrine manner 1.Regulation of angiogenesis during implantation 2.Repressing expression of genes detrimental to pregnancy maintenance : i
- 18. Regulation of decidualprolactin • Most agents known to inhibit or stimulate pituitary prolactin • Secretionincluding dopamine, dopamine agonists, and • do not alter decidual prolactin TRH
- 19. Implantation & Formationof the Placenta & Fetal membrane • Fertilization & Implantation • Biology of the Trophoblast • Embryonic development after implantation • Organization of the placenta • Chorionic villi • Placental development
- 20. • Placenta =Pulmonary,Hepatic, Renal • Hemochorial type of placenta • Fetal-Maternal blood not mixed
- 21. Ovum Fertilization andzygote Cleavage • Ovulation : secondary oocyte Peritoneal cavity oviduct Cilia and tubal peritalsis Fertilization often takes place in ampulla
- 22. Fertilization •Sperm penetrates zonapellucida 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
- 24. • In fallopiantube : 3 days 1st day : Fertilization Zygote : diploid cell 2nd day : 2 cell zygote blastomere thick zona pellucida 3rd day : Morular 16 cells
- 25. • In uterinecavity 4th-5th day Morular = 16 cells Accumulate fluid - between cells Early blastocyst ( 58 cells = 5+53 )
- 26.
- 27. Implantation 1. Apposition :most common occurs on the upper posterior uterine wall 2. Adhesion : Integrins 3. 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
- 28. Trophoblast differentiation • Theformation of the human placenta : trophectoderm • Syncytiotrophoblast : outer multinuclear • Cytotrophoblast : inner mononucear
- 29. Trophoblast differentiation • Afterimplantation is completed, trophoblast differentiates in 2 pathways – Villous trophoblast : chorionic villi – Extravillous trophoblast : decidua , myometrium and maternal vasculature
- 30. 12 th dayafter fertilization Chorionic villi • Primary villi : cytotrophoblast core • Secondary villi : mesenchymal core • Tertiary villi : angiogenesis Villi which failure of angiogenesis >> Hydatidiform mole Anchoring villi • cytrophoblast cells columns • anchore to the decidua at basal plate
- 32. 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
- 33. 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
- 36. Placental development • Modificationof 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
- 37. • Interstitial trophoblast s - penetrate the decidua a nd myometrium - preparation o f vss for endovascular trophoblasts • Endovascul ar
- 38. The chorion • Thechorion 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
- 39. Maternal Regulation ofTrophoblast 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
- 40. • Trophoblasts arefurther secured by fetal fibronectin • Trophoblast glue • presence of fFN in cervical or vaginal fluid is used as a prognostic indicator for preter m labor
- 41. 1. Decidua capsularis 2.Uterine wall 3. Uterine cavity 4. Placenta 5. Decidua parietalis 6. Decidua basalis 7. Chorion leave 8. Embryo 9. Connecting stalk 10. Yolk sac 11. Chorion frondosum 12. Amnion 13. Chorionic cavity 14. Amniotic cavity
- 42. Uteroplacental vasculature Before 12weeks post fertlization Invasion and modification of the spiral a. up to the border of the deciduas and myometrium 12-16 weeks post fertlization Invasion of the intramyometrium segments of spiral a. Remodeling : Dilated , low resistance uteroplacental vessels Significance in the pathogenesis of preeclampsia and IUGR
- 43. 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.
- 44. Placental growth andmaturation • 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
- 45. At term Diameter 185mm Volume 497 ml Thickness 23 mm Weight 508 g Cotyledon : 10-38 lobes (fibrous septa; incomplete partition)
- 46. Placental maturation At term •Thin layer of syncytium • Villi : thin wall capillary • Significant reduction of cytotrophoblasts • Decreased stroma • Increased number of capillary
- 47. Hofbauer cell • Fetalmacrophage • 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
- 48. Changes in placentalarchitecture 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
- 50. Fetal circulation 2 umbillical artery (deoxygenated blood) placenta : chorionic vessels : capillary network in villi Oxygenated blood 1 umbillical vessels
- 51. 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.
- 52. Maternal circulation Basal plate Intervillous space Venous orifice in basal plate Uterine vein
- 53. Maternal circulation (1) Leavematernal circulation (2) Flow into an amorphous space lined by syncytiotrophoblast, rather than capillary end othelium (3) Return through maternal veins without producing arteriovenous-like shunts that would prevent maternal blood from remaining in contact with villi long enough for adequ ate exchange
- 54. • 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 space Principal factors regulating blood flow in the intervillous space •Arterial blood pressure •Intrauterine pressure •The pattern of uterine contractions •Factors that act specifically on arterial walls.
- 55. Breaks in placentalbarrier • 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
- 56. 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
- 57. • 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 Trophoblast only in extravillous cytotrophoblasts in the decidua basalis and in the chorion laeve Embryos used for IVF do not implant if they do not express this soluble HLA-G isoform
- 58. Amnion • the innermost 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
- 59. 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
- 61. Amnion Epithelial Cells Produce •PGE2 >> initiation of labor • fetal fibronectin • tissue inhibitor of metalloproteinase-1 • brain natriuretic peptide • CRH • vasoactive peptide Mesenchymal Cell •Fibroblast layer •Synthesis of - interstitial collagens (majority of tensile strength) - cytokine : IL-6, IL-8, MCP-1
- 62. Metabolic Function • containamniotic fluid • solute & water transport (maintain AF homeostasis) • produce bioactive compounds AMNIOTIC FLUID Increase : until GA 34 weeks At term : 1000 mL
- 63. Umbilical cord • Dorsalsurface 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
- 64. At term •Cord :2 arteries, 1 vein •Rt umbilical v. dissappears early during development •Arteries are smaller than vein Meckel diverticulum : umbilical vesicle remnant, : from umbilicus to intestine The most common vascular anomaly : absence of 1 umbilical artery
- 65. Umbilical cord • Diameter0.8 - 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
- 66. •Wharton jelly - extracellular metrix - a specialized connective tissue - increases in volume at parturition to assist closure of pla cental blood vss
- 67. THANK YOU OFYOUR ATTENTION