The placenta, umbilical cord, and amniotic sac

The placenta, umbilical cord, and amniotic sac protect and provide nutrients to the fetus. The placenta is a fetomaternal organ that enables the selective transfer of nutrients and gases between mother and fetus. The placental barrier limits direct contact between the embryo and maternal blood, thus protecting both mother and child from potentially harmful substances (e.g., blood cell antigens of the unborn, bacteria from the mother). In addition, the placenta produces hormones that mediate maternal adaptation to pregnancy and maintain pregnancy. Establishing uteroplacental circulation involves several steps, including endovascular trophoblast invasion and uterine vascular remodeling. The 50–70 centimeter long umbilical cord connects the placenta with the fetus and contains one umbilical vein that carries oxygenated, nutrient-rich blood supply and two umbilical arteries that carry deoxygenated blood from fetus to the placenta and the maternal circulation. The amniotic sac surrounds the fetus and contains the amniotic fluid, providing mechanical protection to the developing fetus.

Following implantation of the egg, the endometrial stromal cell lining is transformed into the decidua (decidual reaction). The decidua provides nourishment to the conceptus until the definitive placenta forms. Approximately on day 12 of embryonic development, fetal blood vessels come into contact with maternal blood through openings in maternal vessels, forming a region of fetal-maternal exchange.

Decidual reaction

• Decidual reaction: (decidualization): implantation → thickening and structural changes of the endometrium → formation of decidua
• Function of decidua
  • Histiotrophic nutrition
    • Storage of fat and glycogen causes endometrial cell enlargement
    • Secretion of lytic enzymes by the syncytiotrophoblast during invasion of the decidua → nutrient uptake by the syncytiotrophoblast
  • Immune privilege: tight junctions separate the conceptus from adjacent endometrial tissue
  • Preparation for placental circulation: increased progesterone → transformation of decidual vessels into a network of anastomosing spiral arteries (uterine vascular remodeling)
• The decidua has three distinct parts, distinguished by their relation to the site of implantation:
  • Decidua basalis: maternal portion of the placenta
  • Decidua capsularis: decidua that grows over the blastocyst after implantation, appearing as a cap-like structure
  • Decidua parietalis: decidua lining the uterus elsewhere than at the site of implantation

Placentation

Placentation refers to the development of the placenta. The embryonic portion of the placenta is derived from cells of the trophoblast and the maternal portion of the decidua basalis.

• Early placental development
  • Prelacunar stage: until approx. day 9 of embryonic development
  • Lacunar stage
    • From approx. day 9 of embryogenesis
    • Lacunae form in syncytiotrophoblast, these are separated by thin syncytiotrophoblast trabeculae
    • Lytic enzymes of syncytiotrophoblast eventually erode the spiral arteries of the decidua, and maternal blood fills the lacunae.
    • Lacunae merge to form the intervillous space.
    • Hemotrophic nutrition: nutrient supply from maternal blood ^[1]
  • Early villous stage: from approx. day 13–28 of embryogenesis
• Chorionic villi development and maturation: the composition of chorionic villi changes during the course of placental development.
  • Primary villi
    • Develop through migration of cytotrophoblast cells into the syncytiotrophoblast trabeculae
    • Structure
      • Inner layer: cytotrophoblasts
      • Outer layer: syncytiotrophoblast cells with microvilli
  • Secondary villi
    • Develop through migration of extraembryonic mesoderm cells into the center of primary villi
    • Structure
      • Mesenchymal core
      • Inner layer: cytotrophoblast
      • Outer layer: syncytiotrophoblast cells with microvilli
  • Tertiary villi (terminal villi): connect to the umbilical cord vessels during week 3 of embryonic development
    • Tertiary villi develop through vascularization
    • Terminal villi develop after the 4^th month → cytotrophoblast cells begin to disappear → with only isolated cytotrophoblast cells (Langhans cells ) remaining
    • Structure of terminal villi
      • Mesenchymal core with fetal capillaries
      • Inner layer: Langhans cells (isolated cytotrophoblast cells)
      • Outer layer: syncytiotrophoblast

Placental structure

At term, the mature placenta weighs approx. 500 g, is about 2 cm thick, and has a diameter of 15–20 cm. It consists of three parts:

• Basal plate (decidua basalis): mainly maternal component
• Intervillous space and villous trees: fetomaternal zone
• Chorionic plate: fetal component

Basal plate (placenta)

• Description: mainly maternal component, abuts the uterine wall
• Structure: maternal decidua with invading embryonal cells (cytotrophoblast, syncytiotrophoblast, and extravillous trophoblast cells)
• Blood supply: : uterine spiral arteries
  • Placental septa: protrude at several sites in the intervillous space
  • Placental cotyledons: 15–30 separations of the decidua basalis, formed by the placental septa, that can macroscopically be distinguished from each other

Intervillous space and villous trees

• Intervillous space
  • Contact zone between maternal and fetal placental structures (site of fetomaternal gas and nutrient exchange)
  • Filled with maternal blood
  • Contains protruding villous trees
• Villous trees: The placenta is composed of 30–50 branching villous trees.
  • Stem villi: basal region of villous trees with fetal arteries and veins
  • Intermediate villi: region of villous trees with fetal arterioles, venules, and capillaries; important region of gas and nutrient exchange
  • Terminal villi: tertiary villi that float freely in the intervillous space and are directly involved in gas and nutrient exchange
  • Anchoring villi: anchor the villous trees to the decidua
    • The cytotrophoblast of anchoring villi expands and positions itself between the decidua and the syncytiotrophoblast.

Chorionic plate

• Description: : Fetal component of the placenta
• Structure: formed by the syncytiotrophoblast, the cytotrophoblast, and the somatic layer of the extraembryonic mesoderm
  • Chorion frondosum: contains villi, is involved in the formation of the placenta
  • Chorion laeve: outer layer of the fetal placenta, does not contain villi (not involved in the formation of the placenta)

Placental barrier

Maternal and fetal circulation are separated by the placental barrier. The placental barrier controls the gas and nutrient exchange. Until the fourth month of development, the placental barrier consists of six layers. After the fourth month, the cytotrophoblast disappears from the villous wall, leaving only the isolated cytotrophoblast cells (Langhans cells).

• Structure until the 4^th month of embryonic development (from maternal to fetal)
  1. Syncytiotrophoblast
  2. Cytotrophoblast
  3. Basal lamina of trophoblasts
  4. Villous stroma made up of connective tissue
  5. Basal lamina of the endothelium
  6. Capillary endothelium
• Structure from the 4^th month of embryonic development (from maternal to fetal)
  1. Syncytiotrophoblast
  2. Fused basal lamina from trophoblasts and the endothelium
  3. Capillary endothelium

After birth, the placenta must be inspected to ensure it has detached completely from the uterine wall. If this does not occur, there is a risk of postpartum hemorrhage. The check is performed by inspecting for the completeness of all placental cotyledons. On the fetal side, the placenta should be covered by the amnion.

Overview of placental hormones

The most important placental hormones are HCG, HPL, CRH, estrogen, and progesterone; other important hormones during pregnancy include thyroid hormones, oxytocin, and prolactin.

• Site of production: syncytiotrophoblast
• Function of hormones
  • Continuation of pregnancy
  • Maternal adaptation to the pregnancy
  • Regulation of uterine circulation
  • Fetal development and growth
  • Inducing labor

Hormones and the placenta

Gas and nutrient exchange

The placenta is the main site of metabolites and gas exchange between the mother and the fetus.

• Passive transport
  • Diffusion: O₂; , CO₂, creatinine, urea, bilirubin, water, drugs
  • Facilitated diffusion: glucose, lactate
• Active transport: amino acids, peptides, hormones, vitamins, fatty acids, inorganic ions
  • Pinocytosis: proteins, lipids, antibodies (IgG)

Fat-soluble vitamins (A, D, E, K), immunoglobulins (except IgG), and most proteins are either unable to cross the placental barrier or have only limited ability to do so. Vitamin K is an important cofactor for blood coagulation and should be administered to the newborn infant directly after birth.

Anti-D antibodies from the Rhesus system (IgG antibodies) are able to cross the placental barrier. In contrast, isoagglutinins of the ABO system are mainly IgM antibodies, which cannot cross the placental barrier!

The umbilical cord connects the fetus with the fetal part of the placenta (chorionic plate). It typically attaches centrally to the chorionic plate of the placenta. The development of the umbilical cord begins at approx. the 3^rd week of embryonic development. By the end of pregnancy, the umbilical cord is approx. 50–70 cm long.

Formation and structure of the umbilical cord

• The umbilical cord contains 3 allantois-derived blood vessels that carry fetal blood:
  • 2 umbilical arteries: branches from the internal iliac arteries that carry deoxygenated blood from the fetus to the placenta
  • 1 umbilical vein: supplies oxygenated, nutrient-rich blood from the placenta to the fetus (merges into the inferior vena cava via the ductus venosus)

Structure and development of the umbilical cord during early pregnancy

• Connecting stalk: precursor of the umbilical cord
• Content
  • Allantois
    • Small sac-like structure that forms the yolk sac and protrudes into the connecting stalk during the 3^rd week of development
    • The fetal bladder develops at the transition from the allantoic epithelium to the endoderm of the hindgut.
  • Vitelline duct
    • Connects the midgut to the yolk sac
    • Obliterates during 6–7^th week
    • Failure to fully obliterate can lead to the following conditions
      • No obliteration (patent vitelline duct): vitelline fistula (presents with meconium discharge from the umbilicus after birth)
      • Partial obliteration: vitelline cyst (a cystic remnant which can lead to small bowel obstruction if bowel twists around the cyst) or Meckel diverticulum

Structure of the umbilical cord during late pregnancy

• ECM: Wharton jelly (gelatinous connective tissue)
• Cover: amniotic epithelium
• Content:
  • Urachus (duct between fetal bladder and umbilicus)
    • Remnant of the allantois
    • Obliterates after birth to form the median umbilical ligament, covered by the median umbilical fold of the peritoneum
    • Failure to involute may lead to anomalies with an increased risk of malignancy (urachal cancer) and infection.
  • Remnants of the obliterated vitelline duct

The umbilical arteries carry deoxygenated blood, whereas the umbilical vein carries oxygenated blood!

A single umbilical artery is a sign of chromosomal disease and congenital anomalies. ^[2]

Physiological umbilical hernia

Due to the rapid growth of the gastrointestinal tract, there is not enough space within the embryonic abdominal cavity from the 6^th to the 10^th week of development. As a result, sections of the gut herniate into the extraembryonic coelom of the future umbilical cord during this time.

Amniotic cavity

The amniotic sac is formed very early in pregnancy and surrounds the embryo as a protective shell. As the fetus grows, the amniotic cavity expands, eventually resulting in the displacement of the chorionic cavity and the uterine cavity.

• Development: 2^nd week of development through migration of epiblast cells
• Components
  • Lined with amniotic epithelial cells
  • Filled with amniotic fluid, which is produced by amniotic epithelial cells

Amniotic sac

The amniotic sac is composed of maternal (decidua) and fetal components (chorioamniotic membranes) that surround the fetus and provide mechanical protection.

• Amnion
  • Inner amniotic membrane
  • Develops from the embryoblast
  • Secretes amniotic fluid
• Chorion
  • Middle amniotic membrane
  • Develops from the cytotrophoblast
• Decidua
  • Outermost membrane
  • Develops from the decidua capsularis, which lies above the site of implantation

Amniotic fluid

Protective fluid within the amniotic sac that cushions the fetus, prevents adherence of the fetus to the amnion, and serves as a transport medium for nutrients and metabolites.

• Composition: initially a clear liquid
  • Amount: approx. 850–1500 mL by the end of pregnancy (the amniotic fluid is completely exchanged every 3 hours)
  • pH: 7–7.5 (slightly alkaline)
  • Proteins, glucose, urea
  • Fetal urine, lung fluids, hair, dead skin, sebum
  • Vernix: a milky-white, lipid-rich substance that consists of fetal dermal cells and sebaceous gland secretions. It covers the fetus's skin (especially in the third trimester).
• Reabsorption
  • Reabsorption by the amniotic epithelium
  • The fetus swallows approx. 400 mL of amniotic fluid per day, which is excreted through the kidneys.

• Antepartum hemorrhage
• Post-partum hemorrhage
• Rupture of membranes
• Amniotic band syndrome
• Chorioamnionitis
• Placenta previa
• Placental abruption
• Abnormal placental separation