Cleavage

Cleavage is the series of rapid mitotic divisions the zygote undergoes immediately after fertilisation. It is distinctive among mitotic activity in the body because it occurs without any increase in the overall size of the developing conceptus.

In virtually every other context, each daughter cell grows back to about the parent cell's size before the next division. Repeated division therefore produces a tissue that steadily enlarges as cell number increases.

Cleavage does not follow this pattern. The conceptus stays constrained within the zona pellucida, which does not expand, throughout the cleavage period. Successive divisions subdivide the fixed volume of cytoplasm in the original zygote into more and smaller cells.

This is possible because cleavage divisions are essentially the mitotic, chromosome-segregating phase of the cell cycle repeated in rapid succession. There is little of the intervening growth phase that would restore each daughter cell to full size. The conceptus at the end of cleavage is therefore very similar in size to the conceptus just after fertilisation, despite a substantial increase in cell number.

Each cell produced by a cleavage division is termed a blastomere. Successive rounds of cleavage produce steadily more, and progressively smaller, blastomeres.

• The first division, approximately 24 to 30 hours after fertilisation, produces the 2-cell stage.
• The second division produces the 4-cell stage, by around day 2.
• Division continues in this manner, producing the 8-cell stage by around day 3.

Early cleavage divisions are not always perfectly synchronous across blastomeres. Transitional odd-numbered stages are therefore a normal and expected finding, not an abnormality. An example is a 3-cell stage, in which one blastomere of a 2-cell embryo has divided slightly ahead of the other.

In the earliest cleavage stages, individual blastomeres retain totipotency: the capacity, if isolated, to give rise to a complete individual on their own. Developmental potential has not yet become restricted or committed to a specific fate.

This retained totipotency is the embryological basis for monozygotic twinning arising from separation of blastomeres at an early cleavage stage.

It also explains why removing one or a small number of blastomeres for diagnostic testing, as in some forms of preimplantation genetic testing, does not itself impair the developmental potential of the remaining embryo. The remaining blastomeres retain sufficient capacity to continue normal development.

By around day 3 after fertilisation, the conceptus has progressed through the 2-cell, 4-cell, and 8-cell stages and begins to undergo compaction. This distinct structural transition marks the end of the strict cleavage period and the beginning of formation of the morula, the compact cell mass that is the next major preimplantation stage.

The entire cleavage sequence runs from the first division at around 24 to 30 hours after fertilisation to the 8- to 16-cell stage at around day 3. It occurs while the conceptus is actively transported along the uterine tube toward the uterine cavity.

Cleavage and tubal transport are therefore concurrent, overlapping processes, not sequential ones. The conceptus continues through successive cleavage divisions throughout its journey toward the site of eventual implantation.