The Placenta and Fetal Membranes

1
The Placenta and Fetal Membranes

• ????? ????
• R1. ???

2
Fetal Tissues of the Fetal-Maternal Communication
System

• The extravillous and villous traphoblasts
• Placental arm
• The fetal membranes (the amnion-chorion leave)
• Paracrine arm
• Human placenta hemochorioendothelial type

3
(No Transcript)
4
Early Human Development

• Zygote
• Blastomeres
• Morula
• Blastocyst
• Embryo
• Fetus
• Conceptus

5
Fertilization of the Ovum and Cleavage of the
Zygote

• Moore, fig3-5

6

• 58-cell blastocyst
• 107-cell blastocyst
• Fig 5-1

7

• Implantation
• Moore, fig 3-4

8

• 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

9

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

10

• Cytotrophoblasts are the cellular progenitors of
  the syncytiotrophoblast

11

• 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

12
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

13
Current Status of Research

• Expression of the HLA system in trophoblast
  unique set of lymphocytes
• gt may provide explanation for immunological
  acceptance of the conceptus
• ?? trophoblast HLA expression (monomorphic HLA-G
  class I)? uterine large granular lymphocyte
  (LGL)? ???? ??. ??? ??? ???? ??.

14
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

15
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 antigens in the
  trophoblasts

16
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  gt major class I(a) transplantation
  antigens
• three other class I(b) genes
• E, F, G  gt class I HLA antigen
• HLA-G gene

17
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.

18
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.

19
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 tissuee are not in direct contact with
  maternal tissue or blood

20
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

21

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

22
Trophoblast Attachment in Decidua Oncofetal
Fibronectin

• onfFN(oncofetal fibronectin)
• unique glycopeptide of the trophouteronectin
  molecule
• trophouteronectin or trophoblast glue
• formed by extravillous trophoblast, including
  those of chorion laeve
• Function
• a critical role for migration and attachment of
  the trophoblasts to maternal decidua
• facilitates separation of extraembryonic tissues
  from the uterus at delivery

23
Embryonic and Placental Development

• Early Blastocyst
• Trophoblast
• hCG
• Grow expand

24
(No Transcript)
25
Embryonic Development after Implantation
26
(No Transcript)
27
Cytotrophoblast Invasion of Decidual Vessels

• Capillary network
• arterioles
• Spiral arteries

28
(No Transcript)
29
(No Transcript)
30

• Several curious features
• trophoblasts in the vessels lumen do not appear
  to replicate
• these cells are not readily dislodged by flow of
  blood
• these cytotrophoblast 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

31
Organization of Placenta
32

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

33

• 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 circulation? establish?.

34

• 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

35

• Placental Cotyledons
• Certain villi of the chorion frondosum 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 111 ratio of artery to
  vein to cotyledon

36

• 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
  leukocyte s bearing a Y chromosome have been
  identified in women for up to 5 years after
  giving birth to a son

37

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

38

• Placental Aging
• As villi continue to branch and terminal
  ramifications become more numerous and smaller
• gt volume and prominence of cytotrophoblasts
  decrease
• As syncytium thins and forms knots
• gt 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

39

• 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

40

• 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

41
Blood Circulation in the Mature Placenta

• A section through the placenta in situ
• amnion  ?  chorion?  chorionic villi  ?  
  intervillous space ?   decidual plate  ?  
  myometrium

42
(No Transcript)
43
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
• Two umbilical a. separate at the chorionic plate
  to supply branches to the cotyledons

44
Maternal Circulation

• Intervillous space -gt chorionic plate -gt vein
• Spiral a. ? ????, vein? ???? ??
• Ut. Contraction?? vein??
• Intervillous space?? ???? ??? ???? ????
• Ramsey's concept

45

• 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

46
(No Transcript)
47
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

48
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

49
Development
50
(No Transcript)
51
Amnion Cell Histogenesis

• Amnion epithelial cells
• derived from fetal ectoderm (embryonic disc)
• active metabolically synthesis of tissue
  inhibitos of metalloproteinase-1
• Amnion mesenchymal cells
• derived from the embryonic mesoderm
• synthesis of interstitial collagens that make up
  the compact layer of the amnion
• highly capable of synthesizing cytokines - IL-6,
  IL-8, MCP-1
• increased in response to bacterial toxin and IL-1

52
(No Transcript)
53
Anatomy

• Reflected amnion
• Placental amnion
• Umbilical amnion

54
Tensile Strength

• decidua and chorion laeve are quite elastic and
  can expand to twice normal size during pregnancy
• Amnion provides the major strength of the
  membrane
• Tensile strength of amnion resides almost
  exclusively in the compact layer
• composed of cross-linked interstial collagens I,
  III, and lesser amounts of V and VI

55
Metabolic Functions

• solute and water  transport to maintain amnionic
  fluid homeostasis
• produces a variety of bioactive compounds
• vasoactive peptides, growth factors, cytokines
• Amnionic Fluid
• normally clear fluid that collects within the
  amnionic cavity increases in quantity as
  pregnancy advances until near term, when it
  normally decreases
• Average volume of about 1,000 mL is found at term

56
Umbilical Cord and related Structures

• Development

57
Structure and Function

• Umbilical cord, or funis
• fetal umbilicus -fetal surface of the placenta
• diameter 0.8 - 2.0 cm
• average length 55 cm (usual length 30 - 100 cm)
• nodulation , false knot
• Extracellular matrix Wharton's jelly

58
(No Transcript)
59
(No Transcript)
60
(No Transcript)
61
(No Transcript)