PRESENTED BY LT COL(BILQEES)

The Placenta and Fetal Membranes

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

Early Human Development

ZygoteBlastomeresMorulaBlastocystEmbryoFetusConceptus

Fertilization of the Ovum and Cleavage of the Zygote

Moore, fig3-5

58-cell blastocyst107-cell blastocystFig 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

 Cytotrophoblas

tSyncytiotrophoblast

Morphologically uninuclear cells multinuclear giant cells

        cell boders well demarcated lacking

        nucleus single, distinct multiple & diverse

        miotic figure present absent

Origin germinal cell cytotrophoblast

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 설명하고 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 networkarteriolesSpiral 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 day 에 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 day 에 fetal blood vessels are functional & placental circulation 이 establish 됨 .

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 more closely packed

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

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 contentHyrtl anastomosisTwo umbilical a. separate at the chorionic

plate to supply branches to the cotyledons

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

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

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 - IL-6, IL-8,

MCP-1 increased in response to bacterial toxin and IL-1

Anatomy

Reflected amnionPlacental amnionUmbilical 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 homeostasisproduces 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