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Lecture 2 DEVELOPMENT OF PLACENTA. PLACENTA’S MORPHOLOGY AND FUNCTIONS

Lecture 2 DEVELOPMENT OF PLACENTA. PLACENTA’S MORPHOLOGY AND FUNCTIONS. Prof. Vlad TICA, MD, PhD. FETAL TISSUES OF THE FETAL-MATERNAL COMMUNICATION SYSTEM. The extravillous and villous traphoblasts Placental arm The fetal membranes (the amnion-chorion leave) Paracrine arm

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Lecture 2 DEVELOPMENT OF PLACENTA. PLACENTA’S MORPHOLOGY AND FUNCTIONS

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  1. Lecture 2 DEVELOPMENT OF PLACENTA. PLACENTA’S MORPHOLOGY AND FUNCTIONS Prof. Vlad TICA, MD, PhD

  2. FETAL TISSUES OF THE FETAL-MATERNAL COMMUNICATIONSYSTEM • The extravillous and villous traphoblasts • Placental arm • The fetal membranes (the amnion-chorion leave) • Paracrine arm • Human placenta : hemochorioendothelial type

  3. EARLY HUMAN DEVELOPMENT • Zygote • Blastomeres • Morula • Blastocyst • Embryo • Fetus • Conceptus

  4. FERTILIZATION OF THE OVUM AND CLEAVAGE OF THE ZYGOTE

  5. 58-cell blastocyst • 107-cell blastocyst

  6. IMPLANTATION

  7. BIOLOGY OF TROPHOBLAST • Trophoblast is the most variable in structure, function and development • invasiveness provides for attatchment of blastocyst to decidua of uterine cavity • nutrition of the conceptus • function as endocrine organ in human pregnancy • essential to maternal physiological adaptations & maintenance of pregnancy

  8. Differentiation • Cellular, syncytial / uninuclear , multinuclear • Formation of the Syncytium

  9. Cytotrophoblasts are the cellular progenitorsof the syncytiotrophoblast

  10. after apposition & adherence, intrusion of cytotrophoblast between endometrial epithelial cells • this process is facilitated by degradation of the extracellula matrix of endometrium /decidua catalyzed by • urokinase-type plasminogen activator • urokinase plasminogen activator receptor • multiple metalloproteinase • These functions of cytotrophoblasts invading the endometrium are indistinguishable from those of metastasizing malignant cells

  11. IMMUNOLOGICAL ACCEPTANCE OF THE CONCEPTUS • Previous Theories: • antigenic immaturity of the embryo-fetus • diminished immunological responsiveness of the pregnant woman • Decidua: immunologically privileged tissue site • The acceptance and the survival of conceptus in the maternal uterus must be attributed to immunological peculiarity of the trophoblasts, not the decidua

  12. CURRENT STATUS OF RESEARCH • Expression of the HLA system in trophoblast unique set of lymphocytes • may provide explanation for immunological acceptance of the conceptus

  13. IMMUNOCOMPETENCY OF THE TROPHOBLASTS • Many researchers focused on the expression of the major histocompatibility complex (MHC) antigens in trophoblast • MHC class II antigens are absent from trophoblasts at all stages of gestation

  14. TROPHOBLAST HLA CLASS I EXPRESSION • Normal implantation is dependent upon controlled trophoblast invasion of maternal endometrium/decidua and the spiral arteries • a mechanism for permitting and then for limitting trophoblast invasion • Such a system involves the uterine large granular lymphocytes(LGSs) and the unique expression of specific nomomeric HLA class I antigensin the trophoblasts

  15. HLA-I GENE EXPRESSION • HLA genes • the products of multiple genetic loci of the MHC within short arm of chromosome 6 • 17 class I genes have been identified • three classical genes •  A, B, C  => major class I(a) transplantation antigens • three other class I(b) genes • E, F, G  => class I HLA antigen • HLA-G gene

  16. UTERINE LARGE GRANULAR LYMPHOCYTE (LGL) • Believed to be lymphoid and of bone marrow origin and natural killer cell lineage • Present in large numbers only at the midluteal phase of the cycle-at the expected time of implantation in the human endometrium • Near the end of luteal phase of nonfertile ovulatory cycles, the nuclei of LGLs begin to disintegrate • With blastocyst implantation, these cells persist in the decidua during the early weeks of pregnancy • Speculated that LGLs are involved in the regulation of trophoblast invasion

  17. HLA-G EXPRESSION IN HUMAN TROPHOBLASTS • HLA-G antigen • identified only in extravillous cytotrophoblast in decidua basails and chorion laeve • not present in villous trophoblast, either in syncytium or in cytotrophoblasts • expressed in cytotrophoblast that are contiguous with maternal tissue (decidual cell) • It is hopothesized that HLA-G is immunologically permissive of antigen mismatch between mother and fetus

  18. HLA EXPRESSION IN THE HUMAN EMBRYO • as gestation progresses, cells from inner cell mass of blastocyst gradually develop both class I and II HLA antigen • these tissue are not in direct contact with maternal tissue or blood

  19. IMPLANTATION AND INTEGRIN SWITCHING • Apposition, adherence, then intrusion and invasion of the endometrium/decidua by cytotrophoblast (implantation) appears to be dependent upon • trophoblast elaboration of specific proteinases • degrade selected extracellular matrix proteins of the endometrium/decidua • coordinated and alternating process referred to as "integrin switching“ • facilitates migration and then attachment of trophoblasts in the decidua

  20. INTEGRIN • one of four families of cell adhesion molecules (CAMs) • cell-surface receptors that mediate the adhesion of cells to extracellular matrix proteins

  21. TROPHOBLAST ATTACHMENT IN DECIDUA: ONCOFETAL FIBRONECTIN • onfFN(oncofetalfibronectin) • unique glycopeptideof the trophouteronectin molecule • trophouteronectin or trophoblast glue • formed by extravilloustrophoblast, including those of chorionlaeve • Function: • a critical role for migration and attachment of the trophoblasts to maternal decidua • facilitates separation of extraembryonic tissuesfrom the uterus at delivery

  22. EMBRYONIC AND PLACENTAL DEVELOPMENT • Early Blastocyst • Trophoblast • hCG • Grow & expand

  23. EMBRYONIC DEVELOPMENT AFTER IMPLANTATION

  24. CYTOTROPHOBLASTINVASION OF DECIDUAL VESSELS • Capillary network • Arterioles • Spiral arteries

  25. SEVERAL CURIOUS FEATURES • trophoblasts in the vessels lumen do not appear to replicate • these cells are not readily dislodged by flow of blood • these cytotrophoblasts appear to migrate against arterial flow and pressure • no obvious adhesion of these cells one to the other • invasion of maternal vascular tissue bt trophoblasts involves only the decidual spiral arteries, not the veins

  26. ORGANIZATION OF PLACENTA

  27. ORGANIZATION OF PLACENTA • Trophoblast Ultrastructure • Prominent microvilli of the syncytial surface (brush border) • pinocytotic vacuoles and vesicles • absorptive and secretory placental function

  28. ORGANIZATION OF PLACENTA • Chorionic Villi • 12th day • Primary villi • proliferation of cytotrophoblast extend into syncytiotrophoblast • Secondary villi • mesenchymal cord, derived from cytotrophoblast, invade solid trophoblast column • Tertiary villi • after angiogenesis occurs from the mesenchymal cores in situ • 17th day - fetal blood vessels are functional & placental circulationestablished

  29. ORGANIZATION OF PLACENTA • Characteristic of development of H-mole • some villi, in which absence of angiogenesis results in a lack of circulation, may distended with fluid and form vesicles

  30. ORGANIZATION OF PLACENTA • Placental Cotyledons • Certain villi of the chorionfrondosum extend from chorionic plate to the decidua and serve as anchoring villi • Each of the main stem villi (truncal) and their ramifications (rami) constitute a placental cotyledon (lobe) • For each cotyledon, a 1:1:1 ratio of artery to vein to cotyledon

  31. ORGANIZATION OF PLACENTA • Breaks in the Placental "Barrier " • Numerous findings of passage of cells between mother and fetus in both directions • ex) erythroblastosis fetalis • A few fetal blood cells are found in the mother's blood • Fetal leukocytes may replicate in the mother and leukocytes bearing a Y chromosome have been identified in women for up to 5 years after giving birth to a son

  32. ORGANIZATION OF PLACENTA • Placetal Size and Weight • Total number of cotyledons remains the same throughout gestation • Individual cotyledones continue to grow • Placental weights vary considerably

  33. PLACENTAL AGING • As villi continue to branch and terminal ramifications become more numerous and smaller • > volume and prominence of cytotrophoblasts decrease • As syncytium thins and forms knots • > vessels become more prominent and lie closer to the surface • The stroma of the villi • in early pregnancy • branching connective ts. cells are seperated by abundant loose intercellular matrix • later • stroma becomes denser, and the cells more spindly and more closely packed

  34. PLACENTAL AGING • Histologic changes that accompany placental growth and aging are suggestive of increase in the efficiency of transport to and exchange to meet increasing fetal metabolic requirements • decrease in thickness of the syncytium • partial reduction of cytotropholastic cell • decrease in the stroma • increase in the number of capillaries and approximation of these vessels to the syncytial surface • By 4 months: • the apparent continuity of the cytotrophoblast is broken • the syncytium forms knots on the more numerous, smaller villi

  35. PLACENTAL AGING • At term: • Covering of villi may be focally reduced to a thin layer of syncytium with minimal connective tissue • Fetal capillaries seem to abut the tropohoblast • Villous stroma, Hofbauer cells, and cytotrophoblasts are markedly reduced • villi appear filled with thin-walled capillaries • Other changes suggestive of a decrease in the efficiency for placental exchange: • Thickening of the basement membrane of trophoblast capillaries • Obliteration of certain fetal vessels • Fibrin deposition on the surface of villi in basal and chorionic plates as well as elsewhere in the intervillous space

  36. BLOOD CIRCULATION IN THE MATURE PLACENTA • A section through the placenta in situ • amnion → chorion → chorionic villi → intervillous space → decidual plate → myometrium

  37. FETAL CIRCULATION • 2 umbilical arteries • deoxygenated, or "venous-like" blood flows to the placenta • 1 umbilical vein • with a significantly higher oxygen content • Hyrtl anastomosis • 2 umbilical a. separate at the chorionic plate to supply branches to the cotyledons

  38. MATERNAL CIRCULATION • Intervillous space -> chorionic plate -> vein • Spiral a., vein • Ut. Contraction • Intervillous space • Ramsey's concept

  39. THE PRINCIPLE FACTORS REGULATING THE FLOW OF BLOOD IN THE INTERVILLOUS SPACE • arterial blood pressure • intrauterine pressure • pattern of uterine contraction • factors that act specifically upon the arteriolar walls

  40. THE AMNION • Innermost fetal membrane and is contiguous with amnionic fluid • Avascular structure • Provide almost all of the tensile strength of the fetal membranes • protect against rupture or tearing

  41. STRUCTURE • single layer of cuboidal epithelial cells • basement membrane • acellular compact layer • fibroblast-like mesenchymal cells • zona spongiosa • Missing element of human amnion • smooth muscle cell, nerves, lymphatics, blood vessels

  42. DEVELOPMENT

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