Fertilisation and Formation of Zygote

Viability

• Oocyte Viability: The oocyte remains viable up to 24 hours after ovulation.
• Sperm Viability: Sperm can survive in the female reproductive tract for up to 2 days.
• 3-Day Fertility Window: Fertility is highest with intercourse between 2 days before ovulation and 1 day after ovulation.

Fertilisation Process

• Only a small number of sperm reach the uterine tubes, which is the site of fertilisation.
• Capacitation: Before sperm can fertilize the oocyte, they undergo capacitation (increased mobility and fragile acrosomal membranes), triggered by secretions in the female reproductive tract.
• The oocyte is encapsulated by two layers:
  • Corona Radiata: The outermost layer that must be breached.
  • Zona Pellucida: The deeper layer which also needs to be penetrated for sperm entry.

Steps of Sperm Penetration

1. Penetration of Corona Radiata: Sperm, assisted by hyaluronidase, breaks through the corona radiata, causing surrounding cells to disperse.
2. Binding to Zona Pellucida: The sperm binds to the zona pellucida, releasing acrosomal enzymes that digest holes through this layer (many sperm are needed to reach the oocyte membrane).
3. Membrane Fusion: A single sperm fuses with the oocyte membrane, and its nucleus is pulled into the oocyte’s cytoplasm.
4. Cortical Reaction: The oocyte's endoplasmic reticulum releases calcium ions, causing a cortical reaction. This leads to cortical granules releasing enzymes (zonal inhibiting proteins) that:
   • Destroy remaining sperm receptors.
   • Detach any remaining bound sperm.
5. Completion of Meiosis II: The secondary oocyte completes meiosis II, forming an ovum pronucleus and a second polar body.
6. Formation of Male Pronucleus: The successful sperm loses its tail and midpiece, and its nucleus swells, forming the male pronucleus.
7. Fusion of Pronuclei: The male and female pronuclei fuse, creating the zygote (moment of fertilisation).
8. Mitosis Begins: The conceptus starts undergoing mitosis.

Zygote to Blastocyst Implantation

Cleavage and Blastocyst Formation

• Cleavage: Rapid mitotic divisions occur without growth phases, producing smaller cells collectively known as the morula.
• Morula Compaction: Cells of the morula compact, forming an inner cell mass, while fluid accumulates and trophoblast cells develop around the inside of the zona pellucida (forming the early blastocyst).
• Hatching: The zona pellucida starts to break down, allowing the blastocyst to “hatch” from it.

Implantation (6-7 Days After Ovulation)

• Endometrial Receptivity: The endometrium must be in the receptive phase (the height of the secretory stage), regulated by surges of estrogen and progesterone.
• Trophoblast Binding: Trophoblast cells bind to the extracellular matrix of endometrial cells on the uterine wall. The blastocyst may attempt implantation multiple times, detaching and re-floating if the endometrium is immature.
• Endometrial Preparation: The endometrium thickens, blood vessels become more permeable, and inflammatory cells invade the implantation area.
• Trophoblast Differentiation: Trophoblast cells proliferate, forming two distinct layers:
  • Cytotrophoblast: This layer is adjacent to the inner cell mass.
  • Syncytiotrophoblast: A multinucleated layer that invades the endometrium by digesting uterine cells.
• At this stage, the implanted embryo obtains nutrition by digesting endometrial cells.
• Burrowing: The blastocyst burrows through the endometrium and becomes surrounded by a blood pool (lacuna). It is then covered by endometrial cells, sealing it off from the uterine cavity.

Successful Implantation (12 Days After Ovulation)

• Implantation usually takes 5 days, completing around 12 days after ovulation (often around the time menstruation would normally occur).
• Prevention of Menses: To prevent menstruation, trophoblast cells secrete hCG (Human Chorionic Gonadotropin), which signals the corpus luteum to continue producing estrogen and progesterone.
• Chorion Formation: Trophoblast cells differentiate into the chorion, which continues to produce hCG.
• The chorion later develops into the placenta, eventually taking over the corpus luteum's role by producing large amounts of progesterone and estrogen.

Placentation

• Chorion Formation: Cells from the original inner cell mass give rise to a layer of extraembryonic mesoderm, which lines the inner surface of the cytotrophoblast. Together, the cytotrophoblast and extraembryonic mesoderm form the chorion.
• Formation of Germ Layers: The inner cell mass facing the blastocyst cavity develops into a flat disc with three primary germ layers, each giving rise to distinct tissues:
  • Ectoderm: Forms the nervous system, skin, and the amnion. The amnion later fills with fluid, creating the amniotic sac, which surrounds and protects the embryo.
  • Mesoderm: Develops during gastrulation, giving rise to the heart, blood vessels, connective tissue, and other systems.
  • Endoderm: Differentiates into the mucosal linings (epithelial lining) of the gastrointestinal, respiratory, and urogenital tracts.
    • Yolk Sac: Derived from the endoderm, the yolk sac contributes to the development of the digestive tract and produces the earliest blood cells and blood vessels.
    • Allantois: Forms as a structural base for the umbilical cord, facilitating early nutrient and waste exchange between the embryo and placenta.

Organogenesis

• By approximately 8 weeks, all major organ systems are formed, marking the transition to the fetal stage of development.

Development of Chorionic Villi and the Placenta

• Chorionic Villi Formation: The chorion develops fingerlike chorionic villi that extend into the endometrium, creating direct contact with maternal blood. These villi are highly vascularized, allowing for efficient exchange between maternal and fetal blood.
• Lacunae Formation: Large blood-filled spaces, or lacunae, form within the endometrium around the chorionic villi, immersing the villi in maternal blood.
• Endometrial Transformation: The endometrium surrounding the chorionic villi differentiates into two distinct parts:
  • Decidua Basalis: Located on the basal side (next to the stratum basalis, where the umbilical cord will connect), this part of the endometrium anchors the developing placenta. Here, the villi multiply and branch profusely to increase surface area for nutrient and gas exchange.
  • Decidua Capsularis: Found on the luminal side of the embryo, the decidua capsularis expands to accommodate the growing fetus. Villi in this region are gradually compressed as the fetus grows and eventually degenerate.

Placenta Functions

• The placenta serves multiple critical functions for the developing fetus:
  • Nutritive: Transports essential nutrients, including glucose, amino acids, and fatty acids, from maternal blood to the fetus.
  • Respiratory: Facilitates oxygen exchange and removes carbon dioxide from fetal circulation.
  • Excretory: Transfers waste products from the fetus to maternal blood for elimination.
  • Endocrine: Produces hormones necessary for maintaining pregnancy, such as human chorionic gonadotropin (hCG), progesterone, and estrogen.