Early Embryogenesis

Embryogenesis refers to the development of the zygote from fertilization until the end of the eighth week of intrauterine life. It can be categorized into early and late embryogenesis. Early embryogenesis marks the formation of the zygote and concludes with the formation of the primitive streak. This phase is characterized by the production of extra-embryonic structures that are crucial for supporting and nourishing the embryo. Notably, embryos of the same fertilization age may not develop at the same rate. Successful implantation is completed by the end of the second week of development. The following describes major events of early embryogenesis, detailed by day:

Day 8

  • Blastocyst Development: At this stage, the blastocyst is partially embedded in the endometrial stroma.

  • Trophoblast Differentiation: The trophoblast at the embryonic pole further differentiates into two components:

    • Cytotrophoblast: The inner layer composed of individual cells.

    • Syncytiotrophoblast: The outer layer formed by the fusion of cytotrophoblast cells, which facilitates implantation.

  • Inner Cell Mass Differentiation: The inner cell mass, or embryoblast, differentiates into two distinct layers:

    • Hypoblast Layer: Composed of small cuboidal cells.

    • Epiblast Layer: Comprised of high columnar cells, these layers together form a flat disc referred to as the bilaminar germ disc.

  • Amniotic Cavity Formation: The amniotic cavity develops within the epiblast. Amnioblasts, derived from the epiblast, contribute to the formation of the amniotic cavity wall.

Day 9

  • Blastocyst Embedding: The blastocyst is now more deeply embedded in the endometrium.

  • Closure of Implantation Site: A fibrin coagulum forms to close the defect left at the implantation site.

  • Vacuole Formation in Syncytiotrophoblast: Vacuoles appear within the syncytiotrophoblast layer at the embryonic pole. These vacuoles will fuse to create larger spaces known as lacunae, marking the lacunar stage of placental development.

  • Formation of the Primitive Yolk Sac: At the embryonic pole, the primitive yolk sac (exocoelomic cavity) forms from flattened cells likely derived from the hypoblast, resulting in a thin membrane known as Heuser’s membrane or exocoelomic membrane, which outlines the primitive yolk sac.

Days 11 and 12

  • Further Embedding of Blastocyst: The blastocyst becomes entirely embedded in the endometrial stroma, nearly covered by the surface epithelium, and slightly protrudes into the endometrial cavity.

  • Lacunae Communication: The lacunae system forms as communication between the lacunae is established. The syncytial lacunae connect with congested and dilated maternal capillaries, known as maternal sinusoids. Syncytiotrophoblast cells erode maternal sinusoids, allowing maternal blood to flow into the lacunae, leading to the establishment of uteroplacental circulation.

  • Formation of Extraembryonic Mesoderm: Extraembryonic mesoderm forms between the outer surface of the primitive yolk sac and the inner surface of the cytotrophoblast. This mesoderm is derived from yolk sac cells and eventually fills the space between the amnion and cytotrophoblast.

  • Chorionic Cavity Formation: The chorionic cavity, or extra-embryonic cavity, develops when vacuoles within the extraembryonic mesoderm fuse, surrounding the amniotic cavity and primitive yolk sac, except at a critical junction known as the Connecting Stalk, which connects the bilaminar germ disc to the trophoblast layer.

Day 13

  • Healing of Implantation Site: Generally, the implantation site is healed by this day, although occasional bleeding may occur if healing is incomplete (termed implantation bleeding), which can be confused with menstrual bleeding and may mislead gestational dating.

  • Development of Trophoblast Villi: The trophoblast begins developing villous structures (villli), consisting of cellular columns of cytotrophoblast covered by syncytiotrophoblast.

  • Formation of Secondary or Definitive Yolk Sac: Additional cells from the hypoblast will line the interior of the Heuser’s membrane, contributing to the formation of a new space termed the secondary or definitive yolk sac.

  • Exocoelomic Cysts Creation: Portions of the primitive yolk sac are pinched off into the chorionic cavity, creating exocoelomic cysts.

Week 2 (Days 8-14)

  • Chorionic Plate: This refers to the extraembryonic mesoderm lining the inside of the cytotrophoblast.

  • Umbilical Cord Formation: The connecting stalk will develop into the umbilical cord as blood vessels form within the mesoderm.

  • Growth of Bilaminar Germ Disc: The germ disc grows relatively slowly in comparison to the trophoblast, maintaining a small size of only 0.1 to 0.2 mm during early embryogenesis, indicative of the differential growth rates between these two structures.

Clinical Considerations

  • Abnormal Blastocyst Characteristics: There are cases of abnormal blastocysts which may consist solely of syncytium, present with trophoblastic hypoplasia, display abnormal orientation of the germ disc, or show absence of an embryoblast, a condition referred to as a blighted ovum.

  • Hydatiform Mole: This condition is characterized by little to no embryonic tissue; instead, the trophoblast develops and forms a placental membrane. A hydatiform mole can result in a benign tumor, or may progress to a more serious condition, such as a malignant or invasive mole (choriocarcinoma).

  • Genetic Analysis of Moles: Most genetic studies reveal that moles often arise from the fertilization of an oocyte that lacks a nucleus, leading to the duplication of male chromosomes.

  • Other Genetic Disorders: One prominent example includes microdeletion on chromosome 15, which can result in Prader–Willi syndrome when inherited from the father, or Angelman syndrome when inherited from the mother.