The cleavage period represents the first stage of development immediately following fertilization. During this time, the single-celled zygote embarks on a series of rapid mitotic cell divisions. These divisions occur without any overall increase in the embryo’s total volume, which remains constrained within the protective shell of the zona pellucida. This process produces increasingly smaller daughter cells, which are named blastomeres. Cleavage is a rapid subdivision of the zygote’s cytoplasm, serving to increase the number of cells dramatically.
The Initial Rapid Divisions
The initial phases of cleavage are characterized by a swift numerical increase in cells. The first division of the zygote typically occurs about 24 to 30 hours after fertilization, resulting in two blastomeres. These early cells lack the typical growth phases, G1 and G2, found in the normal cell cycle, which is why the overall size of the embryo does not expand. The embryo quickly progresses through the 2-cell, 4-cell, and 8-cell stages over the next two days.
Initially, the divisions may appear roughly synchronous, but they soon become asynchronous, meaning not all blastomeres divide simultaneously. This asynchronous division can result in transient stages with an odd number of cells. A significant biological milestone occurs around the 4-cell to 8-cell stage, called zygotic genome activation, where the embryo’s own genes begin to take control of development. Before this point, development is primarily directed by regulatory proteins and messenger RNA stored in the egg by the mother.
Compaction and the Formation of the Morula
Once the embryo reaches the 8-cell stage, a structural change known as compaction is initiated. Prior to this, the blastomeres are loosely organized and appear spherical. Compaction involves the blastomeres flattening against each other, maximizing the cell-to-cell contact through the formation of specialized adhesion structures. This process is driven by the activation of cell adhesion molecules, particularly E-cadherin, and the establishment of tight junctions between the outer cells.
This tight clustering causes the entire mass to form a solid ball, typically consisting of 12 to 32 cells by approximately day four after fertilization. This structure is called the morula. The process of compaction creates the first distinction between cells that are positioned internally and those on the exterior. This spatial difference prefigures the differentiation into the two major cell lineages of the next stage.
Transition to the Blastocyst
The final step in the cleavage sequence is the transition from the solid morula to the hollow blastocyst. This change begins with a process called cavitation, where the outer cells of the morula actively pump fluid inward. Specialized sodium-potassium pumps create an osmotic gradient, causing water to be drawn into the center of the cell cluster. This accumulation of fluid results in the formation of a large, fluid-filled central cavity known as the blastocoel.
The resulting structure, the blastocyst, typically forms around day five post-fertilization and contains two distinct cell populations. The outer layer of flattened cells surrounding the blastocoel is the trophoblast, which contributes to the formation of the placenta and is necessary for implantation. Clustered at one pole of the blastocoel is the inner cell mass (ICM), or embryoblast, which gives rise to the embryo itself. The formation of the blastocyst marks the end of the cleavage period, as the embryo is ready to shed the zona pellucida and begin implantation.