Fetal Development and Amniotic Fluid Quiz

Placentation and Twinning

• The placenta is a temporary fetomaternal organ
• It forms in the uterus during pregnancy
• It attaches the fetus to the mother's uterine wall via the umbilical cord
• It is highly vascular and endocrine in nature
• The placenta has a circular/discoid shape
• Its purpose is to provide oxygen and nutrients to the fetus, remove waste products of metabolism from the fetus, and secrete hormones necessary for pregnancy maintenance

Placentation: Outline

• Placentation
• Preceding events in 2nd and 3rd week
• Implantation
• Decidua reaction and formation
• Development of the lacunar system in the trophoblast layer
• Development of chorionic villi and formation of the chorion frondosum
• Formation of the placenta proper
• Placental membrane
• Anatomy of the mature placenta
• Functions of the placenta
• Placental circulation
• Fetal membranes and amniotic fluid
• Umbilical cord
• Twinning
• Clinical relevance

Implantation

• About 6 days after fertilization, the blastocyst attaches to the endometrial epithelium, usually adjacent to the embryonic pole
• The trophoblast starts to proliferate rapidly and differentiates into two layers:
  • Cytotrophoblast: a layer of mononucleated cells
  • Syncytiotrophoblast: a highly invasive layer of multinucleated protoplasmic mass with no visible cell boundaries
• Finger-like processes of the syncytiotrophoblast invade the endometrial epithelium and underlying connective tissue of the endometrium.
• By day 9, the blastocyst is deeply embedded in the endometrium
• The penetration defect in the surface epithelium is closed by a fibrin coagulum
• By the 11th-12th day, the blastocyst is completely embedded.
• The blastocyst now produces a slight protrusion into the lumen of the uterus
• Implantation is complete

Decidua Reaction

• The characteristic transformation of the functional endometrial stromal cells following implantation
• The endometrium is in the secretory phase of the menstrual cycle at the time of implantation
• Soon, the syncytiotrophoblast secretes Human Chorionic Gonadotrophin (HCG)
• HCG intensifes changes in the stromal cells, causing them to enlarge, vacuolate, and load with glycogen and lipids.
• These cells become polyhedral and are called decidual cells.
• The reaction initially is confined to the endometrium near the implantation site but spreads throughout the endometrium of the uterus shortly after.
• The functional endometrium is now called the decidua or gravid endometrium.
• The primary function of the decidual reaction is to provide nutrition for the early embryo and provide an immunologically privileged site for the conceptus

### Decidua divisions

• The decidua is subdivided into three parts:
  • Decidua basalis: lies deep to the embryo, anchored to the cytotrophoblastic shell. Consists of a compact layer of large decidual cells.
  • Decidua capsularis: covers the implanted embryo at the abembryonic pole, forming a capsule that separates it from the uterine cavity.
  • Decidua parietalis: the rest of the endometrium

### Second week of development

• Lacunar stage of trophoblast development
• Following implantation, vacuoles appear in the syncytium forming large lacunae
• Lacunae are separated by trabeculae (partitions of syncytium )
• The syncytiotrophoblast appears spongelike
• By the 11th-12th day, lacunar spaces form intercommunicating networks.
• The lacunae networks are more evident at the embryonic pole.
• The syncytiotrophoblast continues to penetrate deeper into the stroma and erode endothelial lining of the maternal capillaries.
• These capillaries (sinusoids) become congested and dilated.
• The mixture of maternal blood, cellular debris from eroded glands enters the lacunar system.
• Maternal blood begins flowing through the trophoblastic system, establishing the primordial uteroplacental circulation
• The trophoblast absorbs nutrients from the lacunar networks and transfers them to the embryo
• By day 13, primary villi formation occurs.
• Each trabecula is initially entirely made of syncytiotrophoblast.
• The cytotrophoblast cells proliferate locally, penetrating the syncytiotrophoblast (trabecula), forming cellular columns surrounded by syncytium.
• These columns are termed primary villi and are surrounded by maternal blood filling the lacunar spaces (now called intervillous spaces).

### Third week of development

• Primary villi begin to branch shortly after appearing.
• The cytotrophoblast invades the primary villi's center/core, becoming secondary villi.
• These secondary villi cover the entire surface of the chorionic sac.
• Mesoderm (mesenchymal) cells differentiate into capillaries and blood cells, becoming tertiary chorionic villi

Third week of development (continued)

• Capillaries in the chorionic villi fuse, forming arteriocapillary networks
• These networks connect with the embryonic heart via vessels that differentiate in the mesenchyme of the chorion
• By the end of the 3rd week, embryonic blood begins flowing through the capillaries in the chorionic villi
• Oxygen and nutrients in maternal blood diffuse through villi walls, entering the embryo's blood
• Carbon dioxide and waste products diffuse from fetal capillaries into the maternal blood through the villi walls
• Cytotrophoblast cells in the apical region of each villus proliferate, crossing the syncytiotrophoblast and forming a continuous layer on the surface of the decidua.
• This layer is called the cytotrophoblastic shell.
• The shell completely isolates the syncytiotrophoblast from the decidua basalis
• Villi, anchoring the chorion to the decidua, are called anchoring villi (stem chorionic villi

Third week of development (continued II)

• Each anchoring villus consists of a stem (truncus chorii, which branches into ramuli chorii)
• The ramuli chorii are attached to the cytotrophoblastic shell
• The anchoring villi sprout free villi into the intervillous space.
• Almost the entire intervillous space becomes filled with villi. This large surface area is for efficient maternal/fetal exchange

Third week of development (continued III)

• Until week 8, villi on the embryonic pole (decidua basalis) extend extensively, forming the chorion frondosum (bushy chorion).
• As the chorionic sac enlarges, the villi on the abembryonic pole degenerate, forming the chorion laeve (smooth chorion).

Placentation: Introduction

• The placenta is a temporary fetomaternal organ.
• It is formed during pregnancy in the uterus.
• It attaches the fetus to the mother via the umbilical cord.
• It is a highly vascular and endocrine organ.
• The placenta has a circular and discoid shape.

Placentation: Formation

• It has two parts with distinct origins:
  • Fetal part: develops from the chorion frondosum
  • Maternal part: develops from the decidua basalis.
• Formation is preceded by events including implantation, development of the lacunae system, decidua reaction, development of chorionic villi, and formation of the chorion frondosum.

Placentation : Formation of placenta proper

• Following anchoring villi formation, septa grow inward from the uterine endometrium into the intervillous spaces.
• These decidual septa divide the placenta into 15-20 lobes called cotyledons.
• Cotyledons do not reach the chorionic plate.
• Each cotyledon comprises 2-3 anchoring villi.

### Placentation: Details of each component

• Each decidual septum has a maternal tissue core covered by syncytial cells.
• This structure ensures maternal blood in the intervillous spaces is separated from fetal tissue of the villi.
• Endometrial (spiral) arteries and veins freely traverse the cytotrophoblastic shell and open into the intervillous spaces.
• The placenta grows and expands, covering approximately 15-30% of the uterus’s internal surface.
• Placental thickening stems from villus arborization, not further penetration into maternal tissue.

Placentation: Membranes/barriers

• Membranes/barriers separate maternal and fetal blood within the placenta
• There is no mixing of maternal and fetal blood in the placenta.
• Exchange of gases, nutrients, and waste occur across the placental barrier.

Placentation:: Blood sources

• Maternal blood from the endometrial arteries fills the intervillous spaces.
• Endometrial veins drain the blood from the intervillous spaces.
• Fetal blood circulates within the fetal blood vessels in the chorionic villi.

Placentation: Membranes thickness

• Until the 20th week, the placental membrane has four layers, measuring approximately 0.025 mm.
• The layers include syncytiotrophoblast, cytotrophoblast, mesoderm of the villus, and endothelium of fetal capillaries.
• After the 20th week, the layers progressively thin out, with the cytotrophoblast disappearing.
• The membrane's thickness then decreases to approximately 0.002 mm, facilitating efficient transport.

### Placentation: Anatomy of mature placenta

• Shape: discoid
• Dimensions: ~15-25cm diameter & ~3cm thickness
• Weight: ~1/6th of the fetal weight (~500-600 grams)
• Fetal surface: covered by the chorionic plate, smooth, and shiny, covered by the amniotic membrane
• Umbilical cord attachment: at the center

### Placentation: Maternal Surface

• The maternal surface has a cobble-stone appearance due to 15-20 rounded elevations (cotyledons) separated by grooves made by decidual septa.
• It’s covered by a thin layer of decidua basalis.

### Placentation: Internal Structure

• The chorionic plate contains chorionic vessels, surrounded by mesoderm and syncytiotrophoblast.
• These vessels are continuous with those in the umbilical cord.

Placental Circulation: Maternal

• Blood enters intervillous spaces via spiral arteries, under pressure, reaching the chorionic plate.
• The blood then circulates around the villi for exchange across the thin placental membrane.
• The blood is drained from the space by veins of the decidua basalis.
• In the fully formed placenta, the 150ml of intervillous blood is replaced every 15-20 seconds (at 3-4 times per minute).

### Placental Circulation: Fetal

• Fetal blood arrives at the placenta through the umbilical arteries.
• Inside the placenta, these arteries ramify freely within the chorion and its branches enter the chorionic villi.
• Veins from the chorionic villi drain into the umbilical vein, carrying oxygen-rich blood and nutrients to the fetus.

Fetal Membranes

• Formation of the amniochorionic membrane is preceded by events, including amnion formation, formation of the chorionic sac and chorion, formation of the decidua capsularis and parietalis, and chorionic villi enlargement.
• The chorion laeve (smooth chorion) forms by the degeneration of chorionic villi on the abembryonic pole of the chorionic sac in later pregnancy.
• The enlarging amniotic cavity obliterates the chorionic sac, and the amnion and smooth chorion fuse to form the amniochorionic membrane.
• The amniochorionic membrane fuses temporarily with the decidua capsularis, eventually adhering to the decidua parietalis.

Amniotic Fluid

• Transparent fluid within the amniotic cavity
• Derived from maternal blood by diffusion across the amniochorionic membrane from the decidua parietalis.
• Also from secretions by amniotic cells, the fetus’s respiratory and digestive tracts (lung, intestine, GI tract), and the fetal kidneys through the fetal urinary tract.
• Is also secreted by the fetal skin before keratinization.

Amniotic Fluid: Volume

• 30ml at 10 weeks
• 450ml at 20 weeks
• ~800–1000 ml at term (~37 weeks).
• Amniotic fluid volume is replaced every 3 hours.

Amniotic Fluid: Function and significance

• Maintains a balanced relationship with the fetal circulation, changing with fetal growth and development
• Large amounts of amniotic fluid pass across the amniochorionic membrane into maternal tissue fluid, entering the uterine capillaries.
• Fetus swallows up to 400ml of amniotic fluid per day (nutrients and waste products exchange)
• Excess amniotic fluid from the fetal kidneys is excreted and returned back to the amniotic sac.
• This process helps maintain fetal homeostasis.
• Acts as a hydrostatic bag (bag of waters) in aiding cervical dilatation at the beginning of labor

Umbilical Cord

• A long cord by which the fetus is attached to the uterine wall via the placenta.  - At term, it is around 50-55cm long and 1-2cm thick.  - Covered by a glistening amniotic membrane.  - Twisted (with a potential for false knots). 
• One end attaches to the center of the anterior abdominal wall of the fetus (umbilical region). 
• The other end attaches to the center of the fetal surface of the placenta.

Umbilical Cord: Formation

• Involves formation of the connecting stalk, the allantoic diverticulum, and the folding of the embryo.
• Incorporation of the yolk sac, vitello-intestinal duct, and allantois into the stalk.
• Development of blood vessels into the umbilical cord also occurs within the stalk. 
• Wharton's jelly forms from the mucoid generation of the mesoderm in the umbilical cord stalk

Umbilical Cord: Contents

• Contains two umbilical arteries and one umbilical vein
• Wharton's jelly
• Remains of allantoic diverticulum
• Remains of the vitellointestinal duct and yolk sac

Umbilical Cord: Function

• The umbilical vein carries oxygenated blood from the placenta to the fetus.
• The umbilical arteries carry deoxygenated blood from the fetus to the placenta.

Twinning

• Multiple pregnancies (2 or more fetuses)
• Twins: two fetuses
• Multiple births are becoming more common due to wider access to fertility treatments.
• Some regions (e.g., Igbo-Ora, Oyo State) have a naturally high twinning rate.
• Higher risks associated with multiple gestations due to the increased number of fetuses.

Twinning: Types (monozygotic and dizygotic)

• Monozygotic (identical) twins: result from a single fertilized ovum/zygote splitting.  - Dizygotic (fraternal) twins: result from the release and fertilization of two ova/oocytes.

Twinning: Monozygotic types

• Early splitting (two-cell stage): dichorionic diamniotic twins (separate chorionic sacs/placentas, separate amniotic sacs).
• Later splitting (early blastocyst stage): monochorionic diamniotic twins (common chorionic sac/placenta, separate amniotic sacs).
• Very late splitting (bilaminar germ disc stage): monochorionic monoamniotic twins (common chorionic sac/placenta, common amniotic sac). 

Twinning: Dizygotic types

• Result from two separate zygotes, with each zygote developing its own embryo, developing its own placenta, amnion, and chorionic sac, and two separate fetuses
• Dizygotic twins are genetically as similar as any two siblings with a shared parentage

Clinical Relevance: Labor/Parturition

• Labour/Parturition: process of fetal and placental expulsion from the uterus.
• Characterized by regular uterine contractions that progressively dilate the cervix.
• Three stages:     1st: Onset of uterine contractions until complete cervical dilation (10 cm).     2nd: Complete cervical dilation to infant delivery.     3rd: Infant delivery to placental delivery.

Clinical Relevance: Placenta delivery

• Placenta expelled 15-30 minutes after infant delivery via the three stages of labor. Placenta separation from the uterine wall due to:
  • Reduction in placental site surface area (uterine muscle contraction)
  • Haematoma formation as spiral arteries close post-delivery.

Clinical Relevance: Uterotonic Agents

• Uterotonic agents, like oxytocin, are administered post-delivery to promote placental separation.
• Signs of separation include lengthening of the umbilical cord, uterus rising in the abdomen, becoming more globular, and a gush of blood

Clinical Relevance: Placental Abruption

• Placental abruption, also called abruptio placentae, involves premature placental separation from the uterine wall.
• This can lead to bleeding and accumulation of blood behind the placenta. Risk factors include uterine tenderness, vaginal bleeding, decreased fetal movement, and shock.

Clinical Relevance: Preeclampsia/Eclampsia

• Preeclampsia is a condition characterized by elevated blood pressure, proteinuria (protein in urine), and edema (fluid retention) in pregnancy.
• Eclampsia is a more severe condition in pregnancy with preeclampsia-associated convulsions
• Placental abnormalities are a contributing factor to the development of preeclampsia/eclampsia.

Clinical Relevance: Placenta Shape Variations

• Placenta shape variations include bilobed (two lobes), multilobular (more than two lobes), diffuse (not disc-shaped), placenta succenturiata (a small separated part of the placenta still connected to the main part), placenta fenestrata (a hole in the placental disc), and circumvallate (peripheral edge of the placenta covered with a circular fold of the decidua).

Clinical Relevance: Umbilical cord abnormalities

• Cord Prolapse: Umbilical cord protruding through the cervix during labor, potentially compressing the cord between the fetal head and maternal pelvic floor, leading to fetal hypoxia
• Prolonged Cord: Cord encircling the fetal neck during delivery, potentially strangling the fetus.
• Shortened Cord: Pulling the placenta away from the uterus during delivery, causing premature separation.
• Cord knots: True knots in the umbilical cord can reduce blood flow and potentially cause fetal hypoxia and death.

Clinical Relevance: Conjoined Twins

• Conjoined twins (Siamese twins): result from incomplete separation of MZ twins.
• They are connected by a tissue bridge, and separation is only possible if vital parts are not shared. The different types of conjoined twins based on the site and extent of fusion are craniopagus (fusion of heads), thoracopagus (fusion of thorax), and cephalthoracopagus (fusion of head and thorax) and pygophagus (fusion of sacral regions).

Clinical Relevance: Twin-Twin Transfusion Syndrome

• Unequal blood distribution in MZ twins from a shared placenta.
• One twin receives too much blood (becoming larger) and the other twin receives insufficient blood (becoming smaller).
• It could potentially lead to death in one or both twins.

Clinical Relevance: Vanishing Twin

• Refers to the death of one twin (often in the first or second trimester).
• The dead twin is resorbed or remains as a compressed dehydrated mass, resembling parchment paper (fetus papyraceus). 

Clinical Relevance: Drug Exposure in Pregnancies

• Drugs and their metabolites cross the placenta, affecting the fetus.
• Substances like alcohol can cause congenital anomalies, and heroin can result in fetal addiction and withdrawal symptoms.
• Certain medications taken during labor or obstetric surgeries can impact the fetus via placental transfer potentially leading to respiratory depression

Clinical Relevance: Prenatal Diagnostic testing

• Amniocentesis: sampling amniotic fluid, often guided by ultrasound, allowing for cell analysis and early diagnosis of chromosomal anomalies (such as trisomy 21 - Down syndrome) and other genetic disorders.

Clinical Relevance: Amniotic Fluid Disorders

• Hydramnios/polyhydramnios: excess amniotic fluid (1500–2000 ml) often related to maternal diabetes or fetal CNS/GIT abnormalities (e.g., anencephaly, esophageal atresia).
• Oligohydramnios: decreased amniotic fluid (<400 ml) potentially related to premature rupture of the amnion, leading to clubfoot or lung hypoplasia. Amniotic bands form when tears in the amnion create fibrous bands that cause ring constrictions and limb amputations.