Transcript The Placenta and Fetal Membranes

The Placenta and Fetal
Membranes
부산백병원 산부인과
R1. 조인호
Fetal Tissues of the FetalMaternal Communication System
• The extravillous and villous traphoblasts
– Placental arm
• The fetal membranes (the amnion-chorion
leave)
– Paracrine arm
• Human placenta : hemochorioendothelial
type
Early Human Development
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Zygote
Blastomeres
Morula
Blastocyst
Embryo
Fetus
Conceptus
Fertilization of the Ovum and
Cleavage of the Zygote
• Moore, fig3-5
• 58-cell blastocyst
• 107-cell blastocyst
• Fig 5-1
• Implantation
– Moore, fig 3-4
• 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
• Differentiation
– Cellular, syncytial/ uninuclear , multinuclear
• Formation of the Syncytium
– Cytotrophoblasts are the cellular
progenitors of the syncytiotrophoblast
Cytotrophoblast
Syncytiotrophoblast
Morphologically
uninuclear cells
multinuclear giant cells
cell boders
well demarcated
lacking
single, distinct
multiple & diverse
present
absent
germinal cell
cytotrophoblast
nucleus
miotic figure
Origin
• 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
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
Current Status of Research
• Expression of the HLA system in
trophoblast unique set of lymphocytes
– > may provide explanation for immunological
acceptance of the conceptus
• 주로 trophoblast HLA expression
(monomorphic HLA-G class I)과 uterine
large granular lymphocyte (LGL)로 설명하
고 있다. 그러나 아직은 완전하지 않다.
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
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
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
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.
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.
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
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
• Integrin
– one of four families of cell adhesion
molecules (CAMs)
– cell-surface receptors that mediate the
adhesion of cells to extracellular matrix
proteins
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
Embryonic and Placental
Development
• Early Blastocyst
– Trophoblast
– hCG
– Grow & expand
Embryonic Development after
Implantation
Cytotrophoblast Invasion of
Decidual Vessels
• Capillary network
• arterioles
• Spiral arteries
• 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
Organization of Placenta
• Trophoblast Ultrastructure
– Prominent microvilli of the syncytial surface
(brush border)
– pinocytotic vacuoles and vesicles
• absorptive and secretory placental function
• Chorionic Villi
– 12th day에 처음 발생
– 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 day에 fetal blood vessels are functional
& placental circulation이 establish됨.
• 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
• 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 1:1:1 ratio of artery to
vein to cotyledon
• 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
• Placetal Size and Weight
– Total number of cotyledons remains the same
throughout gestation
– Individual cotyledones continue to grow
– Placental weights vary considerably
• 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
– 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
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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,
– 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
Blood Circulation in the Mature
Placenta
– A section through
the placenta in situ
• amnion → chorion→
chorionic
villi → intervillous
space → decidual
plate → myometrium
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
Maternal Circulation
• Intervillous space -> chorionic plate ->
vein
• Spiral a. 는 수직으로, vein은 수평으로 주
행
– Ut. Contraction하면 vein차단
– Intervillous space내에 정체되어 모체와 태아
간의 물질교환
• Ramsey's concept
• The principle factors regulating the flow
of blood in the intervillous space
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arterial blood pressure
intrauterine pressure
pattern of uterine contraction
factors that act specifically upon the
arteriolar walls
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
Structure
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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
Development
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 - IL6, IL-8, MCP-1
• increased in response to bacterial toxin and IL-1
Anatomy
• Reflected amnion
• Placental amnion
• Umbilical amnion
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
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
Umbilical Cord and related
Structures
• Development
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