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PLACENTA : TO REGARD OR DISCARD DEPARTMENT OF ANATOMY HIMSR JAMIA HAMDARD, NEW DELHI – 110062 17 TH MARCH, 2015

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PLACENTA : TO REGARD OR DISCARD

DEPARTMENT OF ANATOMY

HIMSR

JAMIA HAMDARD, NEW DELHI – 110062

17TH MARCH, 2015

INTRODUCTION

PROF. RAJ D. MEHRA

INTRODUCTION

• Placenta, a fetomaternal organ that acts as acradle to the developing fetus, while alsoparticipating in fetomaternal tolerance, is aphenomenon that is fascinating, but yet notentirely understood.

• It is the least understood and arguably one of themore important human organs , not only for thehealth of a woman and her fetus duringpregnancy, but also for the lifelong health ofboth.

By increasing the understanding aboutplacenta and our ability to prevent and treatplacental abnormalities, we could improvenot only pregnancy outcome but also healthof the child and of the mother lifelong.

Further, placental function is important forlater health as poor fetal growth is associatedwith higher rates of chronic disease in adultlife.

INTRODUCTION (CONT)

• Placental structure and function affect the health of themother, as seen in the development of insulin resistanceand gestational hypertension, preeclampsia andeclampsia.

• Placental dysfunction affects the fetus, causingprematurity and fetal growth and neurodevelopmentalabnormalities.

• The concept of “placental origins of adult disease” stemsfrom studies where variations in placental developmentaffect the supply of nutrients to the fetus anddevelopment of systems linked to diseases of the adult.

PLACENTA : ABNORMALITIES

• Recent studies indicate that placenta should not be seen as a waste material, but in relation to its important role during pregnancy

• It should be regarded as a great gift from nature as a source of cells and bioactive molecules for therapeutic applications

• Placenta is considered as “the tree of life”, branches of which continue to extend from fetal development and beyond

• Indeed placenta may continue to sustain our life even outside of the womb.

HUMAN PLACENTA

ORGANIZATION OF THE CONTENTS• Introduction• Placental Structure and Development• Placental Anomalies• Clinical Case Correlations• Recent Developments in Placental Research For Healing/Placenta MedicineFor Rejuvenation/Skin CarePlacental MicrobiomePlacenta EncapsulationAs a rich source of Stem Cells

STRUCTURE & DEVELOPMENT OF PLACENTA

DR RANJANA VERMA

Fetal surface • Smooth and shiny. It is covered by amnion.

• The umbilical cord is attached close to the center of the placenta.

• The umbilical vesselsradiate from the umbilical cord.

• They branch on the fetal surface to form chorionic vessels.

Maternal surface

Maternal cotyledons

covered by a thin layer of decidua basalis

Decidual septa

Grooves between the cotyledons

Characteristic Features of Human Placenta

• Labyrinthine

• Hemochorial

• Chorioallantoic

• Deciduate

STRUCTURE OF PLACENTA

It has following components:

• FETAL PART (4/5) Chorion frondosum

• MATERNAL PART (1/5)Decidua basalis

• JUNCTIONAL ZONE Trophoblast and Decidual cells intermingle

STRUCTURE OF UTERINE WALL

LAYERS OF UTERUS•Parametrum•Myometrium•Endometrium (Decidua in pregnancy)

LAYERS OF DECIDUA•Superficial compact layers•Intermediate spongy layer•Basal layer

DEVELOPMENT OF PLACENTA

INNER CELL MASS- Embryo proper

OUTER CELL MASS- Placenta and membranes

• L selectin on trophoblast cells and its carbohydrate receptors on the uterine epithelium mediate initial attachment of the blastocyst to the uterus.

• Integrins- expressed by the trophoblast and the extracellular matrix molecules -laminin and fibronectin.

• Integrin receptors for

• laminin promote attachment,

• fibronectin stimulate migration.

DEVELOPMENT OF PLACENTA

DEVELOPMENT OF PLACENTA

Day 9- Lacunar stageDay 12-Establishment of uteroplacental circulation

Day-13 Primary villi

Day-15 Secondary villi

Projection of syncytiotrophoblastwith core of cytotrophoblast

Core of primary villi invaded with mesoderm

DEVELOPMENT OF PLACENTA

Day-21 Tertiary villi

Fetal capillaries develop in the mesenchymal core of the villi

Cytotrophoblast invade syncytiotrophoblast and makes direct contact with decidua basalis forming anchoring villi

Cytotrophoblast proliferates laterally so that neighbouring outgrowth meet to form spherical cytotrophoblastic shell

DEVELOPMENT OF PLACENTA

CHANGES IN TROPHOBLAST

The trophoblast lineage gives rise to three main cell types in the human placenta:

Syncytiotrophoblast

Villous cytotrophoblast cells

Extravillous cytotrophoblast cells

VASCULAR REMODELLING

As anchoring villi form, single mononuclear cells from extravillous cytotrophoblast infiltrate uterine spiral arteries in two phases-

•In first trimester (10-12 weeks)- Decidua basalis

•In second trimester (16-18 weeks)-Inner one third of myometrium

HYBRID VESSELS- containing both fetal and maternal components

GROWTH OF VILLI

Expansion of the entire conceptus is accompanied by

•Radial growth of the villi

•An integrated tangential growth and expansion of cytotrophoblastic shell

Each villous stem contains-

•Intermediate villi

•Terminal villi (site of fetomaternal exchange)

DEVELOPMENT OF VILLI

Main stem villi-Forms fetal cotyledon

Syncytial sprouts

Intermediate villi

Terminal villi-Lateral projection from main

stem villus

STRUCTURE OF PLACENTABASAL PLATE•Compact and spongy layer of deciduabasalis•Nitabuch’s membrane•Cyotrophoblast•Syncytiotrophoblast

INTERVILLOUS SPACE•Lined by syncytiotrophoblast•Numerous villi project into it from stem villi•Syncytial knots

CHORIONIC PLATE•Mesenchyme containing branches of umbilical vessels•Cytotrophoblast•Syncytiotrophoblast

STRUCTURE OF A PLACENTAL MEMBRANE

Early pregnancy (0.024 mm)•Syncytiotrophoblast•Cytotrophoblast with BM•Mesoderm•Endothelium with BM

Late pregnancy (0.002 mm)•Syncytiotrophoblast•Scanty cytotrophoblast BM•Mesoderm (minimal)•Distended fetal capillaries

PLACENTAL CIRCULATION

Decidual septa-Maternal cotyledon

Main stem villi-Fetal cotyledon

CHORION AND DECIDUA

Decidua basalis- Decidua towards embryonic pole

Decidua capsularis- Decidua towards abembryonic pole

Decidua parietalis- Decidua on the uterine wall

Chorion frondosum-Chorionic villi towards embryonic pole

Chorion laeve- Chorionic villi towards abembryonic pole

PLACENTAL AGEING– Increase in the fibrous tissue in the core of the villous

– Thickening of the basement membrane in the fetal capillary

– Obliteration of some fetal vessels and dialatation of capillaries

– Syncytial knots

– Partial disappearance of cytotrophoblast

– Decrease in mesoderm including hofbauer cell

– Deposition of fibrin on the surface of villi in the junctional zone and chorionic plate

» Decidua-Nitabuch’s membrane

» Intervillous space - white infarct & Rohr’s stria

ABNORMAL PLACENTATION

1. Abnormal implantation

2. Abnormal blastocyst

3. Defect in Nitabuch’s membrane

4. Activated chorion laeve

5. Defect in vascular remodelling

6. Passage across placental membrane/barrier

•Type I Placenta is in lower segment, but the lower edge does not reach internal os

•Type II Lower edge of placenta reaches internal os, but does not cover it

•Type III Placenta covers internal os partially

•Type IV Placenta covers internal os completely

INTRAUTERINE IMPLANTATION

(PLACENTA PREVIA)

1.ABNORMAL IMPLANTATION

1. ABNORMAL IMPLANTATION EXTRAUTERINE IMPLANTATION

(ECTOPIC PREGNANCY)

2. ABNORMAL BLASTOCYST(Hydatidiform mole)

TROPHOBLAST -develops and forms placental membranes

EMBRYOBLAST - little or no embryonic tissue is present

3. DEFECT IN NITABUCH’S MEMBRANE(MORBIDLY ADHERENT PLACENTA)

PLACENTA ACCRETA — chorionic villi attach to the myometrium, rather than being restricted within the deciua basalis

PLACENTA INCRETA — chorionic villi invade into the myometrium.

PLACENTA PERCRETA — chorionic villi invade through the myometrium.

• Placenta succenturiata

• Placenta membranecae

4. ACTIVATED CHORION LAEVE

5. DEFECT IN VASCULAR REMODELLING- PRE ECLAMPSIA

Endovascular invasion of cytotrophoblast into spiral arteries fail to occur beyond deciduo-myometrial junction

6.PASSAGE ACROSS PLACENTAL MEMBRANE

Fetal blood cells escape across placental membrane and there is potential for these cells to elicit antibody response by mother immune systemSome of the blood antigens (Rh) stimulate maternal antibody response against fetal blood cells- ISOIMMUNIZATION

Viruses- Rubella, Cytomegalo, Coxsackei, variola, varicella, Measles, Polio etc.Bacteria- Treponema pallidum, Tubercle bacilliProtozoa- Toxoplama gondii, Malarial parasiteDrugs-

Dr.Shalini KumarAssistant Professor

35 yr old female Presented with spontaneously ruptured

membranes & breech presentation for caesarean delivery at 39wks gestation

Past h/o 2 spontaneus abortion No live issue Surgical h/o dilatation & curettage for

abortions

LSCS was done Baby was delivered Intraoperatively –Irregularity in placental

attachment ~ 2 x2 cm in anterior and medial part of uterus

Area of endometrium surgically corrected to achieve hemostasis

One Hour later in post op ICU ,large clot (approx. 800ml)resulted per vagina on uterine expression

Vitals signs were normal Managed conservatively with fluids and drugs Bleeding continued Intrauterine balloon inserted to tamponade

the bleeding

2 hours later recurrence of perfuse bleeding from vagina with hypotension

2 units of blood trasfused Initially planned for uterine artery

embolisation –>couldn’t be done as vitals were unstable

Shifted to operation theater

Bleeding couldn’t be controlled (>800ml) Exploratory laparotomy,bilateral uterine

artery ligation and supracervicalhysterectomy was performed

Post operative patient was stable Histopathological report showed placenta

increta

Post Partum Haemorrhage following placenta increta

• Primary PPH – Occurs when blood loss is > 500

ml. in the first 24 hours after a vaginal delivery or

greater than 1000 ml after a cesarean birth

(Normal blood loss is about 300 - 500 ml)

• Secondary PPH – significant blood loss

between 24 hours and 6 weeks after birth

• Most cases (99%) of post partum hemorrhage are

primary

Placenta Accreta

Uterine Atony

Lacerations

Retained Placental Fragments

Inversion of the Uterus

Hematomas

Three grades of abnormal placental attachment are defined according to the depth of invasion

Accreta — chorionic villi attach to the myometrium, rather than being restricted within the decidua basalis

Increta — chorionic villi invade into the myometrium

Percreta — chorionic villi invade through the myometrium

Type Description Percent

Placenta accreta

An invasion of the myometrium which

does not penetrate the entire

thickness of the muscle.

75-78%

Placenta increta

Occurs when the placenta further

extends into the myometrium,

penetrating the muscle.

17%

Placenta percreta

The worst form of the condition is

when the placenta penetrates the

entire myometrium to the uterine

serosa. This variant can lead to the

placenta attaching to other organs

such as the rectum or bladder.[9]

5-7%

In this case it is hypothetised that due to previous instrumentation in uterus leads to abnormal attachment of placenta to myometrium resulting in placenta incretawhich was associated with:

Heavy bleeding

Need for transfusion

Required hysterectomy

PRE ECLAMPSIA - ANATOMICAL PERSPECTIVE

Dr SHWETA CHAUDHARY

Pre Eclampsia

Multisystem disorder of unknown etiology characterised by

• Hypertension - blood pressures ≥ 140/90 mm Hg on 2 occasions and

• Proteinuria - with urinary protein excretion ≥ 300 mg/day (in a 24-hour urine specimen) or 100 mg/L

After 20 wks in a previously normotensive and non proteinuric woman

Edema, a classic feature of the disease

HISTORY

A 29 yr old patient came in antenatal clinic with history of two previous pregnancies with a normal outcome and no medical conditions

At 15 weeks, her BMI was 28 ( N- 25)

Blood pressure - 134/86 mmHg

At 27 weeks, she was referred to clinic with new onset hypertension

• BP- 158/102 mmHg• No other sign of pre-eclampsia• No evidence of proteinuria (negative dipstick)• In clinic, her BP settled to 145/90 mmHg

In the 32nd week• Her baby’s estimated fetal weight (EFW) on scan-

appropriate for gestational ageEFW -1,580g

By the 33rd week

• Blood pressure - 156/110 mmHg and

She was administered nifedipine

• Protein: Creatinine Ratio - 24 mg/mmol ( N- < 30 mg/mmol)

She reported headaches, but

• no visual symptoms,

• no coagulopathy, or liver dysfunction

Clinical Question:

Does she have evolving pre-eclampsia?

PLCENTAL GROWTH FACTOR(PlGF)

In the 27th week

• her plasma PlGF was - 34 pg/ml (abnormal <100 pg/mL) suggesting she had placental dysfunction

In the 33rd week

• her plasma PlGF had fallen to

• less than 12pg/ml (very abnormal <12pg/mL) suggesting she had severe placental dysfunction

Pregnancy Outcome:

Two days after commencing nifedipine, her BP decreased to 140/84 mmHg

At 34 weeks, she developed

• Proteinuria (PCR 176 mg/mmol) and a

• USG Scan - IUGR

She was induced, but was delivered by caesarean section for fetal distress.

• Her baby weighed 1,510g

DIAGNOSIS

PRE-ECLAMPSIA WITH SEVERE FETAL GROWTH RESTRICTION DUE TO PLACENTAL

DYSFUNCTION

POG BP(mm Hg) PCR(mg/mmol ) EFW(g) PlGF(pg/ml)

15 weeks 134/86 - - -

27th week 158/102 -ve 1,580 34

33rd week 156/110 24 - 12

34 weeks 140/84 withnifedipine

176 1,510 -

TYPES

• Early-onset PET (diagnosed before 34 weeks of gestation) - necessitates delivery before 34 weeks’ gestation

• Late-onset PET (diagnosed after 34 weeks of gestation) - requires delivery at or after 34 weeks of gestation

• Involves one or more other systems, such as renal, haematological, liver, neurological, pulmonary and/or placental abruption

• Leading cause of maternal and perinatalmorbidity and mortality, particularly when it occurs at a gestational age of less than 34 weeks

DEFECT IN VASCULAR

REMODELLING

• Endovascular cytotrophoblasts fail to

migrate

• Spiral arteries remain as small-caliber

resistance vessels

• Reduction of blood supply to fetoplacental

unit

IUGR

Abnormal placentation in preeclampsia

EXPLANATION• Placental Growth Factor (PlGF) is a member of the

Vascular Endothelial Growth Factor (VEGF) family of growth factors involved in the regulation of angiogenesis

• Expressed by trophoblast cells and placental villi in pregnancy

• Made by the placenta and released into maternal circulation

• Induces vasodilation of uterine, myometrial, mesenteric, and subcutaneous arteries

• Contributes to uterine vascular remodelling during pregnancy

• PlGF increases in first and second trimester and then decreases after 34 weeks suggestive of placental maturity

• Decreased circulating free PlGF during first and second trimester are seen in women diagnosed` with pre-eclampsia

• Low levels of PlGF can be detected before the onset of clinical symptoms

SCREENING PRE ECLAMPSIA

Refrences

• DOI: 10.1161/CIRCULATIONAHA.109.853127

• http://www.plgf.com/home/proposed-clinical-use-of-plgf/case-studies.htm

• http://circ.ahajournals.org/content/128/19/2121.short

RECENT ADVANCES

PROF. RAJ D. MEHRA

Placenta is usually disposed off along with other medical waste, a “forgotten organ” that typically receives little attention from scientists, clinicians, and the public at large.

However, beyond reproductive biology, placentas and associated tissues have been employed in diverse fields such as immunology, stem cell research, environmental sciences and toxicology, genetics, hypertension research, cancer research and tissue engineering.

PLACENTA : NEW APPROACHES

Chemical communications between the placenta and hypothalamus of the mother & fetus play an important role in expression of various genes.

For example, 41 genes expressed in placentas have been associated with neurological diseases.

Two genes: schizophrenia histidine triad nucleotide binding protein 1 (Hint1) and Strathmin1 (Stmn1 have been identified as placental markers for schiziophrenia. (Broad & Keverne 2011; PNAS)

PLACENTA : NEW APPROACHES

PLACENTA: SOURCE OF STEM CELLS

CD34+ve Stem cells have successfully been harvested from the placenta & umbilical cord and differentiated into tissues of choice.

Their potential to treat over 80 diseases to date, including leukemia, Hodgkin's lymphoma, sickle cell anemia and others has been documented.

Although very few placental cell transplants have taken place till date, but this appears to be a promising and upcoming field of research.

www.wombfruits.com

PLACENTA : POSTPARTUM BENEFITS OF PLACENTA CAPSULES

PROPOSED: SCIENTIFIC BASIS OF MATERNAL PLACENTOPHAGY

Placental tissue consumption enhances analgesic effects through a specific endogenous opioid pathway (DiPirro and Kristal 2004; Kristal

1991). Similar hypotheses have been proposed for possible comparable effects in human mothers if they were to engage in the behavior (Apari and Rózsa 2006).

CRH (Corticotropin-Releasing Hormone) Stress Reducer Hypothalamus.

During the last trimester of pregnancy, the placenta secretes so much CRH that the levels in the bloodstream increase threefold.

However, it was also discovered that postpartum women have lower than average levels of CRH, triggering depressive symptoms (NIH study).

PLACENTA : POTENTIAL BENEFITS OF

PLACENTAL CAPSULES IN OTHER DISEASES

Native Americans: dried & ground umbilical cord, given to Child when Sick.

In Central India: women of the Kol Tribe eat placenta to aid reproductive function.

Sino-Vietnamese consume placenta to aid the recovery of those suffering from tuberculosis.

PLACENTA TO THE RESCUE: ROLE DURING STARVATION

Placenta: active protector, not a passive food supply

Starvation (24 hrs)

Alters expression of “imprinted genes”(peg3): unique to mammals

Placenta breaks down its own tissues especially during the phase of brain development

Neuroprotection

Epigenetic signaling from mother to fetus via placenta

(Corbyn 2011; Nature News)

PLACENTREX

A Drug containing Peptides (CRF), Nucleotides (NADPH) & Glutamate is actually derived from an extract of fresh term, healthy, human placenta.

Uses:

• Pelvic Inflammatory disease (Agarwal et al., 2010)

• Wound Healing (Ridley et al., 2003)

PLACENTAL MICROBIOTA: ROLE IN HUMAN HEALTH

Recent evidence suggests that Placenta, long thought to be a sterile organ is home to a bacterial community (non pathogenic, commensal microbiota) similar to the one found in the oral cavity.

Microbes are generally non-pathogenic, however variations in their composition could be the root of common but poorly understood pregnancy disorders such as preterm birth, which occurs one out of every ten pregnancies. (Moskvitch 2014; Nature News)

USE IN COSMETICS

Hydrolyzed Human & animal Placental Proteins have been used as additives in cosmetic products as skin and hair conditioning agents.

Human-derived ingredients are prohibited from use under provisions of the European Union cosmetics & Food and Drug Administration (FDA) based on concerns about transmission of human spongiform encephalopathies and viral diseases eg. human immunodeficiency virus (Nair B, Elmore AR; Cosmetic Ingredient Review Expert panel, 2002)

However, it is widely prevalent in South East Asian countries

MULTIPLE CHOICE QUESTIONS

Dr. Khalid Mehmood

Q1. Uteroplacental circulation is established by which day of development

a) 08th day

b) 10th day

c) 12th day

d) 14th day

Q2.Fetal component of placenta is formed by which of the following

a) Decidua basalis

b) Decidua parietalis

c) Chorion laeve

d) Chorion frondosum

Q3. Most common site of ectopic pregnancy is

a) Ampulla of uterine tube

b) Isthmus of uterine tube

c) Uterine cervix

d) Abdominal cavity

Q4. Exchange between maternal and fetal blood takes place at which of the following site.

a) Main stem villi

b) Intermediate villi

c) Terminal villi

d) Anchoring villi

Q5. Human placenta is

a) Hemochorial

b) Epitheliochorial

c) Endotheliochorial

d) Choriovitelline

KEY

Q1. c

Q2. d

Q3. a

Q4. c

Q5. a