Placenta and fetal membranes

OUR LADY OF FATIMA UNIVERSITYOUR LADY OF FATIMA UNIVERSITY

Department of Obstetrics & GynecologyDepartment of Obstetrics & Gynecology

Placenta & Fetal MembranesPlacenta & Fetal Membranes

Crisostomo S. O. Ordoño Jr. MDCrisostomo S. O. Ordoño Jr. MD



DeciduaDecidua

SpecializedSpecialized

Highly modifiedHighly modified



DeciduaDecidua

Dependent on:Dependent on:

EstrogenEstrogen

ProgesteroneProgesterone

Blastocyst ImplantationBlastocyst Implantation



Decidua of PregnancyDecidua of Pregnancy

Structure based on anatomical location:Structure based on anatomical location:

Decidua BasalisDecidua Basalis

Decidua CapsularisDecidua Capsularis

Decidua ParietalisDecidua Parietalis



DeciduaDecidua

Decidua VeraDecidua Vera

14 – 16 weeks AOG14 – 16 weeks AOG



DeciduaDecidua

Layers of the Decidua Parietalis & BasalisLayers of the Decidua Parietalis & Basalis

Zona CompactaZona Compacta

Zona SpongiosaZona Spongiosa

Zona BasalisZona Basalis



Decidua ReactionDecidua Reaction

Commences mid-luteal Commences mid-luteal phasephase

Completed with Completed with Blastocyst ImplantationBlastocyst Implantation



DecidualDecidual

Decidual ReactionDecidual Reaction

Endometrial Stromal Endometrial Stromal CellsCellsEnlarge, polygonalEnlarge, polygonalRound & vesicular nucleiRound & vesicular nucleiClear & basophilic cytoplasmClear & basophilic cytoplasmPericellular membranePericellular membrane



DeciduaDecidua

Pericellular Membrane provides:Pericellular Membrane provides:

Attachment for the Attachment for the TrophoblastTrophoblast

Protection against Protection against proteasesproteases



DeciduaDecidua

Blood Supply:Blood Supply:

Decidua ParietalisDecidua Parietalis

Decidua CapsularisDecidua Capsularis




Decidual HistologyDecidual Histology

True Decidual CellsTrue Decidual Cells

Endometrial StromaEndometrial Stroma

Bone Marrow Derived Bone Marrow Derived CellsCellsEndometrial large Endometrial large granular lymphocytesgranular lymphocytes



DeciduaDecidua

Zona SpongiosaZona Spongiosa

Large distended glands Large distended glands with hyperplasia minimal with hyperplasia minimal stromastroma

Becoming cuboidal to flat Becoming cuboidal to flat in later pregnancyin later pregnancy



DeciduaDecidua


Spongy zone is mainly Spongy zone is mainly arteries & veinsarteries & veins

Invaded by interstitial Invaded by interstitial trophoblast & giant cellstrophoblast & giant cells



DeciduaDecidua

HistologyHistology

Nitabuch’s Layer/ Nitabuch’s Layer/ Fibrinoid DegenerationFibrinoid Degeneration

Rohr Stria found at the Rohr Stria found at the bottom of the intervillous bottom of the intervillous space & surrounding the space & surrounding the anchoring villianchoring villi



DeciduaDecidua

Prolactin productionProlactin production

Produced by the same Produced by the same gene in the pituitarygene in the pituitary

Identical amino acid Identical amino acid sequencesequence

Different promoter to Different promoter to initiate transcriptioninitiate transcription



DeciduaDecidua

Role of ProlactinRole of Prolactin

Maintenance of AF Maintenance of AF volumevolume

Regulate immune Regulate immune function in the deciduafunction in the decidua

Regulate angiogenesisRegulate angiogenesis



Fertilization & ImplantationFertilization & Implantation



107 - cell Blastocyst107 - cell Blastocyst

Stage of release from the Stage of release from the zona pellucidazona pellucida

Due to proteases from Due to proteases from the secretory the secretory endometriumendometrium

Blastocyst directly Blastocyst directly influence the receptivity influence the receptivity of the endometriumof the endometrium



Receptivity of the EndometriumReceptivity of the Endometrium

Cytokines from Cytokines from the Blastocystthe Blastocyst

EstrogenEstrogen

ProgesteroneProgesterone



Endometrial ResponseEndometrial Response

Leukemia Inhibiting Leukemia Inhibiting FactorFactor

Colony Stimulating FactorColony Stimulating Factor

Effect: increase Protease secretion by Trophoblast Effect: increase Protease secretion by Trophoblast to degrade the extracellular matrixto degrade the extracellular matrix



ImplantationImplantation

Occurs within 6 – 7 days Occurs within 6 – 7 days post fertilizationpost fertilization

Must be on Days 20 – 24 Must be on Days 20 – 24 of the endometrial – of the endometrial – ovarian cycleovarian cycle

Apposition is the 1Apposition is the 1stst step of implantation step of implantation



Biology of the TrophoblastBiology of the Trophoblast



Trophoblast DifferentiationTrophoblast Differentiation

88thth day Post Fertilization day Post Fertilization

Trophoblast differentiates into:Trophoblast differentiates into:

Primitive Primitive SyncytiotrophoblastSyncytiotrophoblast

Primitive mononuclear Primitive mononuclear CytotrophoblastCytotrophoblast



Primitive CytotrophoblastPrimitive Cytotrophoblast

Germinal cells of the Germinal cells of the syncytiumsyncytium

Well-demarcated cell Well-demarcated cell borderborder

Can undergo DNA Can undergo DNA synthesissynthesis



Primitive SyncytiotrophoblastPrimitive Syncytiotrophoblast

Multi-nucleatedMulti-nucleated

No individual cellsNo individual cells

Lacks the ability for DNA Lacks the ability for DNA synthesissynthesis



Trophoblast DifferentiationTrophoblast Differentiation

Villous TrophoblastVillous Trophoblast

Extravillous TrophoblastExtravillous Trophoblast



Villous TrophoblastVillous Trophoblast

Gives rise to the Gives rise to the chorionic villichorionic villi

Function:Function:Transport of oxygen & Transport of oxygen & nutrientsnutrients



Extravillous TrophoblastExtravillous Trophoblast

Migrates to the decidua & Migrates to the decidua & myometriummyometrium

Gives rise to the primary Gives rise to the primary villous stalkvillous stalk

Penetrates the maternal Penetrates the maternal vasculaturevasculatureInterstitial trophoblastInterstitial trophoblastEndovascular Endovascular trophoblasttrophoblast



Interstitial TrophoblastInterstitial Trophoblast

Penetrates the maternal Penetrates the maternal decidua & myometriumdecidua & myometrium

Surrounds the maternal Surrounds the maternal spiral arteriesspiral arteries



Endovascular TrophoblastEndovascular Trophoblast

Penetrates the lumen of Penetrates the lumen of the spiral arteriesthe spiral arteries



Trophoblast InvasionTrophoblast Invasion

1010thth day the blastocyst is day the blastocyst is totally encased within the totally encased within the deciduadecidua

Similar invasion Similar invasion characteristic of characteristic of metastatic cancer cellsmetastatic cancer cells



ChorionChorion

Trophoblast with an Trophoblast with an underlying mesenchymeunderlying mesenchyme



VilliVilli

Primary VilliPrimary Villi

Secondary VilliSecondary Villi

Tertiary VilliTertiary Villi



Placental OrganizationPlacental Organization

Hemochorial PlacentationHemochorial Placentation

Hemo: maternal Blood Hemo: maternal Blood bathing the bathing the SyncytiotrophoblastSyncytiotrophoblast

Chorio: Chorio:

Chorion PlacentaChorion Placenta



Langhan’s CellsLanghan’s Cells

Inner layer of Inner layer of cytotrophoblast in a cytotrophoblast in a chorionic villichorionic villi



Anchoring VilliAnchoring Villi

Proliferation of Proliferation of trophoblast at the tip that trophoblast at the tip that is anchored to the is anchored to the deciduadecidua



Chorionic PlateChorionic Plate

Formed by 8 – 10 weeksFormed by 8 – 10 weeks

When amnion & When amnion & mesenchyme of chorion mesenchyme of chorion fuse togetherfuse together

HemodichorialHemodichorial

HemomonochorialHemomonochorial



Placental DevelopmentPlacental Development



Development of the Chorion & Development of the Chorion & DeciduaDeciduaBlastocystBlastocyst

Outer pole expands Outer pole expands towards the endometrial towards the endometrial cavitycavity

Inner pole forms the Inner pole forms the placentaplacenta



Inner PoleInner Pole

Composed of the villous Composed of the villous trophoblast & anchoring trophoblast & anchoring cytotrophoblastcytotrophoblast

Chorionic villi proliferate Chorionic villi proliferate to form the chorionic to form the chorionic frondosumfrondosum



Outer PoleOuter Pole

Forms the chorion laeveForms the chorion laeve

Due to the degeneration Due to the degeneration of the villi in contact with of the villi in contact with the decidua capsularisthe decidua capsularis

More translucent than the More translucent than the amnionamnion

Composed of Composed of cytotrophoblast and cytotrophoblast and mesenchymemesenchyme



AmniochorionAmniochorion

Formed by the union of Formed by the union of the amnion and chorionthe amnion and chorion

Site of molecular transfer Site of molecular transfer & metabolic activity& metabolic activity

Paracrine Arm of the Paracrine Arm of the Fetal-Maternal Fetal-Maternal Communication SystemCommunication System




Due to its ability to Due to its ability to secrete proteolytic secrete proteolytic enzymes to digest the enzymes to digest the extracellular matrixextracellular matrix

And activate proteinases And activate proteinases already present in the already present in the endometriumendometrium




Ability to invade in the 1Ability to invade in the 1stst trimester and limited trimester and limited Invasiveness in the last trimester is controlled by:Invasiveness in the last trimester is controlled by:

Autocrine & Paracrine Autocrine & Paracrine Trophoblastic Trophoblastic

Endometrial FactorsEndometrial Factors




TrophoblastTrophoblast

Insulin – like growth Insulin – like growth FactorFactor

Acts in an autocrine Acts in an autocrine mannermanner

Promotes invasion into Promotes invasion into the endometriumthe endometrium




Decidual CellsDecidual Cells

Insulin like growth factor Insulin like growth factor binding protein type 4binding protein type 4

Blocks the autocrine loopBlocks the autocrine loop

HENCE: controlled HENCE: controlled invasivenessinvasiveness




Secured by Fetal FibronectinSecured by Fetal Fibronectin

Oncofetal Fibronectin or Oncofetal Fibronectin or Fetal-Specific FibronectinFetal-Specific Fibronectin

A Trophoblastic GlueA Trophoblastic Glue



Decidual Spiral Artery InvasionDecidual Spiral Artery Invasion

Carried out by two populations of Extravillous Carried out by two populations of Extravillous Trophoblast:Trophoblast:


Endovascular Endovascular TrophoblastTrophoblast





Aggregates around the Aggregates around the maternal spiral arteriesmaternal spiral arteries

Prepares the arteries to Prepares the arteries to facilitate invasionfacilitate invasion



Decidual Spiral Artery InvasionDecidual Spiral Artery InvasionEndovascular TrophoblastEndovascular Trophoblast

Enters the lumen of the Enters the lumen of the spiral arteriesspiral arteries

Initially forming cellular Initially forming cellular plugsplugs

Destroys the Destroys the endotheliumendothelium

Fibrinoid material Fibrinoid material replaces muscle and replaces muscle and connective tissueconnective tissue




Does not involve the Does not involve the Decidua ParietalisDecidua Parietalis

Decidual Veins are not Decidual Veins are not invadedinvaded




Stages of Uteroplacental Vessel Development Stages of Uteroplacental Vessel Development

11stst Stage StageBefore 12 weeks AOGBefore 12 weeks AOGInvasion & Modification Invasion & Modification of Spiral Arteriesof Spiral Arteries




Stages of Uteroplacental Vessel DevelopmentStages of Uteroplacental Vessel Development

22ndnd Stage StageBetween 12 – 16 weeksBetween 12 – 16 weeksInvasion of Invasion of intramyometrial parts of intramyometrial parts of the spiral arteriesthe spiral arteriesProducing low-Producing low-resistance vesselsresistance vessels



Establishment of Maternal Blood Establishment of Maternal Blood FlowFlow

Occurs approximately 4 Occurs approximately 4 weeks post fertilizationweeks post fertilization



Villus BranchingVillus Branching

Some become Some become anchoring villianchoring villi

Majority would arborize Majority would arborize and end freely in the and end freely in the intervillous spaceintervillous space

Each truncal villi and Each truncal villi and ramification is one ramification is one lobule/ cotyledonlobule/ cotyledon

Each lobule has one Each lobule has one artery and veinartery and vein



Placental Growth & MaturationPlacental Growth & Maturation



Placental GrowthPlacental Growth

1717thth week AOG placenta week AOG placenta & fetal weights are & fetal weights are approximately equalapproximately equal

At Term, placenta is 1/6 At Term, placenta is 1/6 of the fetal weight of the fetal weight



Placental DimensionsPlacental Dimensions

DiameterDiameter185 mm185 mm

ThicknessThickness23 mm23 mm

VolumeVolume497497

WeightWeight508 grams508 grams



Placental MaturationPlacental Maturation

Stroma of the VilliStroma of the Villi

Abundant and loose Abundant and loose intracellular matrix early intracellular matrix early in gestationin gestation

Later becomes dense Later becomes dense and cells more spindly and cells more spindly and closely packedand closely packed

Infiltration of Hofbauer Infiltration of Hofbauer cellscells




Hofbauer CellsHofbauer Cells

Fetal MacrophagesFetal Macrophages

Increase in number and Increase in number and maturation as pregnancy maturation as pregnancy progressprogress

Capable of paracrine Capable of paracrine regulation of Trophoblast regulation of Trophoblast FunctionFunction




Histological Changes that provides an increased Histological Changes that provides an increased efficiency of transport & exchangeefficiency of transport & exchange

Decrease in thickness of Decrease in thickness of the syncytiumthe syncytium

Decrease StromaDecrease Stroma

Increase VascularityIncrease Vascularity



Fetal & Maternal Blood Circulation in Fetal & Maternal Blood Circulation in Mature PlacentaMature Placenta



Fetal CirculationFetal Circulation

Deoxygenated Blood Deoxygenated Blood flows through two flows through two umbilical arteriesumbilical arteries

Umbilical vessels branch Umbilical vessels branch repeatedly beneath the repeatedly beneath the amnion and diving villiamnion and diving villi

Blood with a higher O2 Blood with a higher O2 content passes thru the content passes thru the umbilical veinumbilical vein




Placental Surface / Chorionic vesselsPlacental Surface / Chorionic vessels

Umbilical vessels along Umbilical vessels along the fetal surface of the the fetal surface of the chorionic platechorionic plate

Responsive to vasoactive Responsive to vasoactive substancessubstances

Arteries always cross Arteries always cross over the veinsover the veins




Truncal ArteriesTruncal Arteries

Perforating branches of Perforating branches of the surface arteriesthe surface arteries

Each supply one Each supply one cotyledoncotyledon

Decrease amount of Decrease amount of smooth muscle but has smooth muscle but has increase in caliberincrease in caliber



Maternal CirculationMaternal CirculationPhysiological Maternal-Placental CirculationPhysiological Maternal-Placental Circulation

Maternal blood thru the Maternal blood thru the basal plate and driven basal plate and driven high up to the chorionic high up to the chorionic plateplate

Blood flows back down Blood flows back down as it baths the as it baths the microvillous surfacemicrovillous surface

Maternal blood drains Maternal blood drains back to the venous back to the venous orificesorifices



Maternal – Placental CirculationMaternal – Placental Circulation

Factors Regulating Blood FlowFactors Regulating Blood Flow

Arterial Blood PressureArterial Blood Pressure

Intrauterine PressureIntrauterine Pressure

Pattern of Uterine Pattern of Uterine ContractionsContractions

Factors acting on the Factors acting on the arterial wallarterial wall



Immunological ConsiderationsImmunological Considerations

The acceptance and survival of the conceptus in the The acceptance and survival of the conceptus in the maternal uterus must be attributed to: maternal uterus must be attributed to:

Immunological peculiarity Immunological peculiarity of the Trophoblastof the Trophoblast



Immunogenicity of the TrophoblastImmunogenicity of the Trophoblast

Major Histocompatibility Major Histocompatibility complex (MHC) class I complex (MHC) class I and II antigens are and II antigens are absent from villous absent from villous trophoblasttrophoblast

Making it appear Making it appear immunologically Inertimmunologically Inert

But invasive But invasive cytotrophoblast express cytotrophoblast express MHC class I moleculesMHC class I molecules



Trophoblast HLA (MHC) Class I Trophoblast HLA (MHC) Class I ExpressionExpression

“normal implantation is dependent on controlled trophoblastic invasion of maternal endometrium-decidua and spiral arteries”

Moffett-King (2002)



Trophoblast HLA (MHC) Class I Trophoblast HLA (MHC) Class I ExpressionExpression

Human Leukocyte Antigens Express by the Human Leukocyte Antigens Express by the TrophoblastsTrophoblasts

Classical HLA - CClassical HLA - C

Non Classical HLA - ENon Classical HLA - E

Non – Classical HLA - GNon – Classical HLA - G



AmnionAmnion

Provides almost all of the Provides almost all of the tensile strength of the tensile strength of the fetal membranesfetal membranes



Amnion StructureAmnion StructureSingle layer of epithelial Single layer of epithelial cells-ectoderm derivedcells-ectoderm derived

Basement membraneBasement membrane

Acellular Compact Layer Acellular Compact Layer composed of interstitial composed of interstitial collagencollagen

Fibroblast-like Fibroblast-like mesenchymal cellsmesenchymal cells

Acellular zona Acellular zona spongiosaspongiosa



Amnion DevelopmentAmnion DevelopmentAmniogenic cells – Amniogenic cells – precursor of amnionic precursor of amnionic epitheliumepithelium

Growth of the amnion Growth of the amnion eventually engulfs the eventually engulfs the embryo and prolapses embryo and prolapses into the cavityinto the cavity

End of the 1End of the 1stst trimester – trimester – apposition of the apposition of the mesoblast of the chorion mesoblast of the chorion and amnionand amnion



Amnion Epithelial CellsAmnion Epithelial Cells

Major site of transfer Major site of transfer between AF and amnionbetween AF and amnion

Metabolically ActiveMetabolically Active



Metabolic Activity of the AmnionMetabolic Activity of the Amnion

Inhibits metalloprotinase-Inhibits metalloprotinase-1 synthesis1 synthesis

Produce PGE2 & Fetal Produce PGE2 & Fetal FibronectinFibronectin

Site of Prostaglandin Site of Prostaglandin productionproduction

Synthesis of vasoactive Synthesis of vasoactive peptidespeptides



Vasoactive peptides produced by the Vasoactive peptides produced by the AmnionAmnion

Endothelin - Endothelin - vasoconstrictorvasoconstrictor

Parathyroid – related Parathyroid – related protein - protein - vasodilatorvasodilator

Brain natriuretic peptide Brain natriuretic peptide – – smooth muscle relaxantsmooth muscle relaxant

Corticotrophin – Corticotrophin – Releasing Hormone – Releasing Hormone – smooth muscle relaxantsmooth muscle relaxant



Importance of the Metabolic Activity Importance of the Metabolic Activity of the Amnionof the Amnion

Modulates chorionic Modulates chorionic vessel tone and blood vessel tone and blood flowflow

Availability to the fetus of Availability to the fetus of the bioactive agentsthe bioactive agents



Amnion AnatomyAmnion Anatomy

Placental AmnionPlacental Amnion

Umbilical Cord AmnionUmbilical Cord Amnion



Amnion Tensile StrengthAmnion Tensile Strength

Exclusively resides in the Exclusively resides in the compact layercompact layer

Composed of x-linked Composed of x-linked collagens I & IIIcollagens I & III



Metabolic FunctionMetabolic Function

Maintain AF homeostasisMaintain AF homeostasis

Production of bioactive Production of bioactive agentsagents

Sensitive to mechanical Sensitive to mechanical stretching:stretching:Triggers autocrine & Triggers autocrine & paracrine responsesparacrine responses



Amnionic FluidAmnionic Fluid

Clear fluidClear fluid

Continuously increase Continuously increase amount until 34 weeksamount until 34 weeks

Average Volume :Average Volume :

1,000 ml at term1,000 ml at term



Umbilical Cord & Related StructuresUmbilical Cord & Related Structures



Cord Structure & FunctionCord Structure & Function

Extends from the fetal Extends from the fetal umbilicus to the fetal umbilicus to the fetal surface of the placentasurface of the placenta

Dull whiteDull white

MoistMoist

Covered by amnionCovered by amnion



Cord Structure & FunctionCord Structure & Function

Contains :Contains :2 arteries2 arteries1 vein1 vein

Diameter: 0.8 – 2.0 cmDiameter: 0.8 – 2.0 cm

Average Length: 55 cmAverage Length: 55 cm

Wharton jelly : Wharton jelly : extracellular extracellular matrixmatrix



Thank You!Thank You!

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Placenta and fetal membranes