Embryology | Development of the Placenta

Key Concepts

• Placenta Development: Cleavage, implantation, trophoblast differentiation, extraembryonic coelom formation, chorionic villi development, decidua interaction.
• Trophoblast Differentiation: Cytotrophoblast, syncytiotrophoblast.
• Chorionic Villi: Primary, secondary, tertiary villi.
• Placental Structure: Chorionic plate, chorionic frondosum, decidua basalis, cotyledons, intervillous spaces.
• Placental Function: Gas exchange, nutrient delivery, waste removal, hormone production (estrogen, progesterone, HCG, human placental lactogen, relaxin, corticotropin-releasing hormone).
• Maternal-Fetal Interface: Amniotic membrane, chorionic membrane, decidua capsularis, decidua parietalis.

Placenta Development

Cleavage and Blastocyst Formation

• Zygote Formation: Sperm fertilizes secondary oocyte in the ampulla of the fallopian tube, forming a zygote surrounded by the zona pellucida.
• Cleavage Stages: Zygote undergoes cleavage, progressing through 2-cell, 4-cell, 8-cell, and 16+ cell (morula) stages, all within the zona pellucida.
• Morula to Blastocyst: Water influx into the morula creates a fluid-filled cavity (blastocoel), forming the blastocyst.
• Blastocyst Structure: The blastocyst consists of the outer cell mass (trophoblast) and the inner cell mass (embryoblast).
  • Trophoblast: Forms the placenta.
  • Embryoblast: Forms the embryo (ectoderm, mesoderm, endoderm).

Implantation

• Uterine Lining: Endometrium (decidua), myometrium, and perimetrium. Blastocyst should only invade the endometrium.
• Decidualization: Transformation of stratum functionalis and stratum basalis cells into decidual cells, filled with glycogen and lipids.
  • Decidua Basalis: Part of the endometrium that replicates and proliferates.
  • Decidua Functionalis: Part where the blastocyst attaches and invades.
• Placenta Accreta/Increta/Percreta: Abnormal placental invasion beyond the decidua basalis, into the myometrium (increta), or beyond (percreta).
• Initial Attachment: Trophoblast microvilli attach to pinopods on the endometrial lining, providing a loose attachment.
• Stronger Attachment: Integrins on the trophoblast bind to selectins (and sometimes collagen) on the endometrium.
• Chemokine Stabilization: Trophoblast cells release chemokines to stabilize the adherence mechanism, allowing invasion into the stroma.

Trophoblast Differentiation

• Differentiation: Trophoblast differentiates into two layers:
  • Cytotrophoblast: Inner layer of cells.
  • Syncytiotrophoblast: Outer multinucleated layer formed by fusion of cytotrophoblast cells.
• Syncytiotrophoblast Function:
  • Releases hydrolytic enzymes to break down stromal tissue for invasion.
  • Secretes human chorionic gonadotropin (HCG) to stimulate the corpus luteum to produce progesterone, maintaining the endometrial lining.

Embryoblast Differentiation

• Bilaminar Disc: Embryoblast differentiates into the bilaminar disc:
  • Epiblast: Layer adjacent to the amniotic cavity.
  • Hypoblast: Layer adjacent to the primary yolk sac.

Lacunae Formation

• Lacunae Formation: Syncytiotrophoblast forms spaces (lacunae) within the stromal tissue.
• Blood Filling: Syncytiotrophoblast releases proteolytic enzymes that break down uterine blood vessels, filling the lacunae with blood, forming intervillous spaces.

Extraembryonic Mesoderm and Coelom Formation

• Extraembryonic Mesoderm: Hypoblast cells (and sometimes the yolk sac) produce extraembryonic mesoderm between the cytotrophoblast and the amniotic cavity/primary yolk sac.
• Chorion Formation: Extraembryonic mesoderm contributes to the formation of the chorion, the fetal component of the placenta.
• Extraembryonic Coelom: Spaces form within the extraembryonic mesoderm, creating the extraembryonic coelom (chorionic cavity).
• Mesoderm Layers: The extraembryonic mesoderm splits into two layers:
  • Somatopleuric Extraembryonic Mesoderm: Outer layer associated with the cytotrophoblast.
  • Splanchnopleuric Extraembryonic Mesoderm: Inner layer associated with the amniotic cavity and primary yolk sac.
• Connecting Stalk: Connects the somatopleuric and splanchnopleuric layers.

Chorionic Villi Formation

• Primary Villi: Cytotrophoblast cells proliferate and extend through the syncytiotrophoblast, forming primary villi.
• Outer Cytotrophoblastic Shell: Cytotrophoblast cells penetrate through the syncytiotrophoblast and surround the intervillous spaces, forming the outer cytotrophoblastic shell.
• Secondary Villi: Somatopleuric extraembryonic mesoderm invades the primary villi, forming secondary villi.
• Tertiary Villi: Mesodermal cells within the secondary villi differentiate into capillaries, forming tertiary villi.
• Umbilical Cord Formation: The connecting stalk, composed of extraembryonic mesoderm, develops into the umbilical cord, containing two umbilical arteries and one umbilical vein.
• Blood Vessel Development: Umbilical arteries branch into chorionic arteries on the chorionic plate, which then branch into cotyledon arteries within the chorionic villi.

Placental Structure and Exchange

• Tertiary Villi Structure: Extraembryonic mesoderm (with blood vessels) surrounded by cytotrophoblast, surrounded by syncytiotrophoblast.
• Maternal-Fetal Exchange: Exchange of gases, nutrients, and waste products occurs across the syncytiotrophoblast, cytotrophoblast, chorionic mesoderm, and fetal blood vessel endothelium.
• Cotyledon Formation: Decidua tissue forms septa that separate tertiary villi into compartments called cotyledons (15-20).
• Cytotrophoblast Regression: After 20 weeks, the cytotrophoblast layer regresses, thinning the placental membrane for more efficient exchange.

Placental Linings

• Chorionic Frondosum: Extensive tertiary villi structure derived from the chorionic plate, interacting with the decidua basalis.
• Decidua Basalis: Maternal component of the placenta, interacting with the chorionic frondosum.
• Placenta Formation: Chorionic frondosum (fetal) + decidua basalis (maternal) = placenta.
• Amniotic Membrane: Innermost membrane surrounding the fetus.
• Chorionic Membrane: Surrounds the amniotic membrane.
• Decidua Capsularis: Surrounds the chorionic membrane.
• Decidua Parietalis: Part of the decidua not directly involved with the placenta.
• Fusion: As the fetus grows, the decidua capsularis fuses with the decidua parietalis, obliterating the uterine cavity.
• Chorionic Laeve: Part of the chorion without extensive villi, forming a thin membrane.

Placental Functions

Metabolic Functions

• Gas Exchange: Oxygen delivery to the fetus and carbon dioxide removal.
• Nutrient Delivery: Glucose, amino acids, fatty acids, water-soluble vitamins, and IgG antibodies.
• Waste Removal: Urea, uric acid, and other waste products.
• Passive Immunity: Transfer of IgG antibodies from mother to fetus for protection against pathogens.
• Rh Incompatibility: Potential for maternal IgG antibodies against Rh-positive fetal red blood cells to cause erythroblastosis fetalis. RhoGAM is administered to Rh-negative mothers to prevent sensitization.
• Torch Infections: Transmission of pathogens across the placenta, including toxoplasmosis, other (HIV, syphilis, hepatitis B), rubella, cytomegalovirus (CMV), herpes simplex virus (HSV), and Zika virus.

Hormonal Functions

• Estrogen and Progesterone: Produced by the placenta after 10-12 weeks, maintaining the endometrial lining, promoting fetal development, and forming the mucus plug.
• Thyroid Hormone: Promotes development of the central nervous system.
• Human Placental Lactogen (HPL): Decreases insulin sensitivity in the mother, promotes lipolysis and gluconeogenesis, providing glucose and fatty acids for the fetus.
• Relaxin: Relaxes ligaments of the pubic symphysis, widening the pelvic inlet and outlet for delivery.
• Corticotropin-Releasing Hormone (CRH): Stimulates cortisol production, which is crucial for fetal lung development and surfactant production.
• Infant Respiratory Distress Syndrome (IRDS): Can occur if premature infants are born before adequate surfactant production, leading to alveolar collapse.