Cleavage: Early Embryonic Development

Cleavage: Early Embryonic Development

• Cleavage is the first major event after fertilization, occurring approximately 24 hours post-fertilization.
• Mammalian cleavage differs from lower vertebrates due to the placental connection. The lack of yolk storage in mammalian eggs necessitates a reliance on maternal nutrients.
• Mammalian eggs are small, allowing for rapid cell divisions that convert the one-celled zygote to a multicellular embryo.
• Cell divisions during cleavage are not perfectly synchronous, resulting in embryos with an odd number of cells.
• Each cell division takes about 12-24 hours.
• No growth occurs during cleavage; the embryo remains at roughly 0.1 mm in diameter.
• The rapid increase in cell number occurs exponentially, following a pattern where the total cell number increases faster than the size.

Cleavage Events

• Cleavage involves rapid mitotic divisions without growth phases.
• Blastomeres (the resulting daughter cells) progressively decrease in size with each division.
• Blastomeres at the 8-cell stage are totipotent, meaning they can develop into a complete organism, crucial for twinning.
• The process culminates in the formation of a morula, a solid ball of cells.
• Subsequently, the morula forms a blastocyst, a hollow ball of cells.

Blastocyst Formation and Cavitation

• Cavitation is the formation of a fluid-filled cavity within the blastocyst known as the blastocoele.
• This process is driven by sodium (Na+) transport mediated by sodium-potassium pumps (Na+/K+).
• Sodium and water accumulate between inner blastomeres, creating the blastocoele.
• Cavitation leads to the differentiation of the blastocyst into an inner cell mass (embryoblast) and an outer cell mass (trophoblast).

Compaction and Cell Adhesion

• Compaction occurs at the 8-cell stage, where blastomeres adhere more tightly together.
• This results in a compact morula structure.
• E-cadherin, a calcium-dependent cell adhesion protein, plays a crucial role in mediating compaction.
• E-cadherin is essential for cell adhesion during compaction. Silencing of the epithin gene prevents compaction.

Blastocyst Differentiation

• The inner cell mass (ICM), also known as the embryoblast, will develop into the embryo proper.
• The outer cell mass, also known as the trophoblast, forms the fetal placental contribution. The trophoblast is crucial for embryonic interactions with the mother and providing protection and delivering nutrients.

Molecular Regulation of Cleavage

• Key genes and proteins regulate early embryonic development.
• Nanog, Oct-4, Sox-2, and Cdx-2 are critical regulators.
• Nanog maintains the integrity of the inner cell mass (ICM).
• Oct-4 (OCT-4) is associated with the pluripotency of cells.
• Sox-2 regulates gene expression in the ICM post-8 cell stage.
• Cdx-2 is essential for trophoblast differentiation.
• LIF (Leukemia Inhibitory Factor) is also important for implantation and early embryonic development.

Implantation

• Implantation begins approximately 6-7 days after fertilization.
• The uterus is prepared by hormones to receive the embryo.
• The blastocyst adheres, penetrates, and becomes embedded in the uterine endometrium (the uterine lining).
• The decidual reaction is a significant part of implantation, involving the transformation of endometrial stromal cells into decidual cells, supporting the implanting embryo.

Twinning

• Dizygotic twins originate from two eggs and two sperm.
• Monozygotic twins originate from a single fertilized egg that splits into two embryos.
• Splitting occurs earlier, around the 8-cell stage.
• Conjoined twins (parapagus, ischiopagus, etc.) represent incomplete splitting.

Zona Pellucida and Hatching

• The zona pellucida plays a critical role in early embryonic development, preventing premature implantation.It restricts entry of sperm and acts as a protective filter.
• The blastocyst hatches from the zona pellucida before implantation occurs.

Ectopic Pregnancy

• Ectopic pregnancies occur when implantation occurs outside the uterus.
• Tubal ectopic pregnancies, where the blastocyst implants in a fallopian tube, are the most common type.