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Zygote Cleavage

Fissio

For medical students2 min readUpdated 2026-10-10

Zygote cleavage is a series of consecutive mitotic divisions of a fertilized egg without an intervening period of cell growth. This process produces new cells called blastomeres, while the embryo travels down the uterine tube toward the uterus while maintaining its original volume.

First DivisionCompleted 30–32 hours post-fertilization
Cleavage TypeHoloblastic, uneven, and asynchronous in humans
Lack of GrowthThe cell cycle practically lacks the $G_1$ pre-synthetic phase
End of Day 4A morula of 32 blastomeres is formed

Cell Cycle and Metabolic Features

The process starts in the lumen of the uterine tube and finishes when the embryo enters the uterine cavity. In the early stages, a thick zona pellucida (fertilization envelope) remains around the embryo. It acts as a rigid barrier: it prevents the overall volume from increasing and blocks the influx of external nutrients. All vital activity relies exclusively on internal reserves.

Because the total volume is fixed, daughter cells become smaller with each new cycle. The cell cycle practically lacks the $G_1$ phase (the growth phase prior to DNA synthesis). Meanwhile, the number of nuclei grows, along with the mass of DNA and chromosomal proteins. Conversely, the cytoplasmic fraction per cell drops sharply. The biochemical meaning of this phenomenon is that maternal cytoplasmic components are actively recycled into nucleotides for DNA construction and amino acids for histone synthesis.

Human Cleavage Specifics

Human embryonic cleavage is characterized by three key features:

Shortly after the process begins, the cells separate into two pools with different functions. Dark, large blastomeres divide slowly and become precursors to the embryoblast (from which the body of the fetus will form). Light, small blastomeres divide very rapidly and form the trophoblast, the cell layer responsible for uterine implantation and subsequent nutrition.

Chronology of Development: From Zygote to Blastocyst

The increase in cell number is strictly tied to the time elapsed since fertilization:

  1. First two days (early stage): the first division (two-blastomere stage) is completed in 30–32 hours. By 40 hours, the embryo consists of four cells.
  2. Day 3 (72 hours): the embryo counts 12 to 16 cells.
  3. Day 4: the morula is formed. This is a dense cellular mass lacking an internal cavity, resembling a mulberry. It consists of 32 blastomeres: roughly 3–4 are slow dark cells (having undergone 2 division cycles), and the remaining 27–28 are fast light cells (having undergone about 5 cycles).
  4. Days 4 to 6 (late stage): at the 4–4.5 day mark (58 cells) and by 5.5 days (107 cells), the blastocyst forms—an embryonic vesicle containing a fluid-filled cavity.

Biological Potency of Cells

During the first two to three divisions, blastomeres retain totipotency; each possesses equal potential and can give rise to an entire organism. If cells dissociate (split) at this stage, it leads to the birth of monozygotic twins.

However, at the 8–16 blastomere stage, totipotency is lost. Synthetic processes activate within the cells, they begin to visually diverge, and differentiation is triggered. Under natural conditions, totipotency is retained exclusively by the precursor cell of primordial germ cells.

In experimental medicine, totipotency can be induced artificially. To achieve this, specific protein transcription factors are introduced into differentiated tissue cells. The genetic potential can also be realized through cloning by transplanting somatic cell nuclei into an enucleated zygote (stripped of its own nucleus). Success rates are highest when the nuclear donors are stem cells rather than regular somatic cells.

Mnemonic

To remember the human cleavage pattern, use the acronym HUA: Holoblastic, Uneven, Asynchronous.

Frequently asked questions

What types of zygote cleavage (aside from holoblastic unequal) exist in other chordates?

In other chordates, besides holoblastic unequal cleavage, sources indicate:

  • Holoblastic, equal, synchronous — in invertebrates and primitive chordates.
  • Meroblastic (incomplete) cleavage — in teleost fishes, reptiles, and birds; only the animal (apical) pole divides. In the classification of incomplete cleavage for fish, reptiles, and birds, the discoidal type is specified.
  • Holoblastic, partially unequal, asynchronous — in mammals.
What types of blastulae are formed as a result of different cleavage types?

Sources indicate the following matches between cleavage type and blastula type:

  • Coeloblastula — from holoblastic, equal, synchronous cleavage.
  • Amphiblastula — from holoblastic, unequal, asynchronous cleavage.
  • Discoblastula — from meroblastic (incomplete) cleavage.
  • Blastocyst — from holoblastic, partially unequal, asynchronous cleavage in mammals.
Why does the total volume of the embryo not increase during cleavage?

A thick zona pellucida remains around the embryo, physically restricting growth and blocking the uptake of external substances. The cells simply divide the existing volume of cytoplasm, becoming smaller.

Where do materials for DNA synthesis come from if the embryo does not feed?

The egg's own reserves serve as building materials. Cytoplasmic components are actively broken down and converted into nucleotides for new DNA and amino acids for histone molecules.

At what stage can monozygotic twins appear?

This is possible during the first 2–3 divisions. At this stage, cells are totipotent, and if accidentally separated, each blastomere can develop into a full, independent organism.

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