The placenta, umbilical cord, and amniotic sac
Development of uteroplacental circulation
Following implantation, the endometrial lining is transformed (decidual reaction). The decidua provides nourishment to the embryo until the definitive placenta forms. Approximately on day 12 of embryonic development, fetal blood vessels (through opening of the maternal vessels) come into contact with maternal blood, forming a region of fetal-maternal exchange.
Decidual reaction
- Decidual reaction (decidualization): implantation → thickening and structural changes of the endometrium → formation of decidua
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Function of decidua:
- Histiotrophic nutrition: storage of fat and glycogen causes cellular enlargement → secretion of lytic enzymes by syncytiotrophoblast during invasion of the decidua → nutrient uptake by syncytiotrophoblast
- Immune privilege: tight junctions separate the conceptus from adjacent endometrial tissue
- Preparation for placental circulation: under the influence of progesterone, decidual vessels transform into a network of anastomosing spiral arteries (uterine vascular remodeling)
- The decidua has three distinct parts, which are distinguished according to 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 pregnant 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 from the decidua basalis.
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Early placental development:
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Prelacunar stage:
- Until approx. day 9 of embryogenesis
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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, causing maternal blood to fill the lacunae.
- Lacunae merge to form the intervillous space.
- Hemotrophic nutrition: nutrient supply from maternal blood
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Early villous stage:
- From approx. day 13–28 of embryogenesis
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Prelacunar stage:
- During the course of placental development, the composition of chorionic villi changes.
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Chorionic villi development and maturation:
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Primary villi
- Develop through migration of cytotrophoblast cells into the syncytiotrophoblast trabeculae
- Structure:
- Inner layer: cytotrophoblast
- Outer layer: syncytiotrophoblast cells with microvilli
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Secondary villi
- Develop through the migration of extraembryonic mesoderm cells into the center of primary villi
- Structure
- Mesenchymal core
- Inner layer: cytotrophoblast
- Outer layer: syncytiotrophoblast cells with microvilli
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Tertiary villi (terminal villi): connect to the umbilical cord vessels during week 3 of development
- Tertiary villi develop through vascularization
- Terminal villi develop after the 4thmonth → cytotrophoblast cells begin to disappear → only isolated cytotrophoblast cells (Langhans cells ) remain
- Structure of terminal villi
- Mesenchymal core with fetal capillaries
- Inner layer: isolated cytotrophoblast cells (Langhans cells)
- Outer layer: syncytiotrophoblast
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Primary villi
The placenta
Placental structure
At the end of pregnancy, 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 (decidual basalis) (mainly maternal component)
- Intervillous space and villous trees (fetomaternal zone)
- Chorionic plate (fetal component)
Basal plate (decidual basalis)
- Mainly maternal component of the placenta, abuts the uterine wall
- Structure: maternal decidua with several ingrown embryonal cells (cytotrophoblast, syncytiotrophoblast, and extravillous trophoblast cells )
- Supplied by uterine spiral arteries
- Placental septa: protrude at several sites in the intervillous space
- Placental cotyledons: 10–40 areas at the side facing the uterine wall that can macroscopically be distinguished from each other
Intervillous space and villous trees
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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
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Villous trees: 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
- Terminal villi: tertiary villi that float freely in the intervillous space and are directly involved in gas and nutrient exchange
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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
- Fetal component of the placenta
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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 barriers consists of five layers. After the fourth month, the cytotrophoblast disappears from the villous wall, leaving only the isolated cytotrophoblast cells (Langhans cells).
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Structure until the 4th month (from maternal to fetal)
- Syncytiotrophoblast
- Cytotrophoblast
- Basal lamina of trophoblasts
- Villous stroma made up of connective tissue
- Basal lamina of the endothelium
- Capillary endothelium
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Structure from the 4th month (from maternal to fetal)
- Syncytiotrophoblast
- Fused basal lamina from trophoblasts and the endothelium
- 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!
Placental function
Hormone production
- Site of production: Syncytiotrophoblast
- Function of hormones
- The most important hormones are HCG, HPL, CRH, estrogen, and progesterone
Hormone | Site of production | Effect(s) | Course during pregnancy |
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hCG (human chorionic gonadotropin) |
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hPL (human placental lactogen) |
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Estrogen |
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Progesterone |
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Thyroid hormones |
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Oxytocin |
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Prolactin |
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Gas and nutrient exchange
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Passive transport
- Diffusion: O2 , CO2, creatinine, urea, bilirubin, water, drugs
- Facilitated diffusion: glucose, lactate
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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 an 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 means that they are unable to cross the placental barrier!
The umbilical cord
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. Development of the umbilical cord begins at approx. the 3rd week of embryogenesis. 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 blood vessels that carry fetal blood:
- 2 umbilical arteries: branches from the abdominal arteries and internal iliac artery that return deoxygenated blood 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)
Early stage in the development of the umbilical cord
- Connecting stalk: precursor of the mature umbilical cord
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Content
- Allantois (small sac-like structure that protrudes into the connecting stalk)
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Vitelline duct: joins the midgut to the yolk sac
- Obliteration during 7th week
- A failed obliteration leads to vitelline fistula (no obliteration), or meckel diverticulum (partial obliteration)
Late stage in the development of the umbilical cord
- Ground substance: gelatinous connective tissue (Wharton jelly)
- Cover: amniotic epithelium
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Content:
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Urachus (duct between fetal bladder and umbilicus)
- Remnant of the allantois
- Obliterates after birth to form the median umbilical ligament.
- Remnants of the obliterated vitelline duct
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Urachus (duct between fetal bladder and umbilicus)
The umbilical arteries carry deoxygenated blood, whereas the umbilical vein carries oxygenated blood!
Physiological umbilical hernia
Due to their rapid growth, there is a short period of time during which there is not enough space for the abdominal within the embryonic abdominal cavity. As a result, sections of the gut herniate into the extraembryonic coelom of the future umbilical cord from the 6th–10th week of development.
Amnion and amniotic cavity
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, which eventually results in the obliteration of the chorionic cavity and the uterine cavity.
- Development: 2nd week of development through migration of epiblast cells
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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) which surround the fetus and provide mechanical protection.
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Amnion: inner amniotic membrane
- Develops from the embryoblast and secretes amniotic fluid
- Chorion: middle amniotic membrane
- Develops from the cytotrophoblast
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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
- Hair, dead skin, sebum
- Fetal urine
- 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/day of amniotic fluid per day, which is excreted through the kidneys.
Clinical significance
- Antepartum hemorrhage
- Post-partum hemorrhage
- Rupture of membranes
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Placental abruption disorder
- Abnormally deep penetration of the trophoblast (e.g., placenta accreta) → problems with the placenta separating from the uterine wall
- Cytotrophoblastic shell malformation → severe bleeding complications.