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Histology · Early stages of human intrauterine development

Zygote cleavage

Fissio

Zygotic cleavage is a series of successive mitotic divisions of a fertilized egg cell that occur without a period of cell growth. This results in the formation of new cells (blastomeres) while the embryo moves through the oviduct toward the uterus, maintaining its initial volume.

First divisionCompleted 30–32 hours after fertilization
Type of cleavageIn humans, it is holoblastic, unequal, and asynchronous
Without growthThe cell cycle practically lacks the $G_1$ presynthetic period
End of day 4A morula of 32 blastomeres is formed
4 min readFor medical studentsUpdated 09/24/2026
Material prepared by WhiteCoat Pro editorial team based on platform study guidesReviewed by medical editor: Aulov A. A., general practitioner · 09/24/2026

Cell cycle and metabolism features

The process begins in the lumen of the oviduct and finishes when the embryo enters the uterine cavity. In the early stages, a thick fertilization envelope persists around the embryo. It acts as a rigid barrier, preventing an increase in total volume and blocking the uptake of external nutrients. All metabolic activity relies solely on internal reserves.

Since the total volume is fixed, daughter cells become smaller with each new division cycle. Their cell cycle virtually lacks the $G_1$ phase (the growth phase prior to DNA synthesis). Meanwhile, the number of nuclei increases, accompanied by an increase in DNA mass and chromosomal proteins. Conversely, the proportion of cytoplasm per cell drops sharply. The biochemical significance of this phenomenon is that maternal cytoplasmic components are actively recycled into nucleotides for DNA synthesis and amino acids for histone synthesis.

Specifics of human cleavage

The human embryo is characterized by three key cleavage features:

  • Holoblastic: absolutely all cells of the embryo undergo cleavage.
  • Unequal: the resulting blastomeres vary in size (forming larger and smaller cells).
  • Asynchronous: cells do not divide simultaneously. Due to varying division rates, intermediate stages with an odd number of blastomeres (e.g., 3 or 5) may occur.

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

Test your knowledge on the topicTasks from the Histology course bank — instant answers and explanations.

Developmental timeline: 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 30–32 hours later. By 40 hours, the embryo consists of four cells.
  2. Third day (72 hours): the embryo contains 12 to 16 cells.
  3. Fourth day: the morula is formed. This is a dense, solid cell mass lacking an internal cavity, resembling a mulberry. It consists of 32 blastomeres: about 3–4 of these are slow dark cells (having undergone 2 division cycles), while the remaining 27–28 are fast light cells (having undergone about 5 cycles).
  4. Days four through six (late stage): at the 4–4.5 day mark (58 cells) and by 5.5 days (107 cells), the blastocyst is formed, representing an embryonic vesicle containing a fluid-filled cavity.

Biological potency of cells

During the first two to three divisions, blastomeres retain totipotency, meaning each possesses equal potential and is capable of giving rise to an entire organism. If cells dissociate (separate) at this stage, it leads to the birth of monozygotic twins.

However, at the 8–16 blastomere stage, totipotency is lost. Synthetic processes are activated in the cells, they begin to morphologically differentiate, and lineage commitment is initiated. Under natural conditions, totipotency is retained only by the precursor cells of the primordial germ cells.

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

Briefly: answers to topical questions

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

In other chordates, aside from holoblastic unequal cleavage, sources indicate:

  • Holoblastic, equal, synchronous — in invertebrates and primitive chordates.
  • Meroblastic cleavage — in teleost fish, reptiles, and birds; only the apical part cleaves. The discoidal type is specified in the classification of meroblastic cleavage for fish, reptiles, and birds.
  • Holoblastic, partially unequal, asynchronous — in mammals.

What types of blastulae are formed as a result of different cleavage types?

Sources indicate the following correspondences between cleavage types and blastula types:

  • Coeloblastula — with holoblastic, equal, synchronous cleavage.
  • Amphiblastula — with holoblastic, unequal, asynchronous cleavage.
  • Discoblastula — with meroblastic cleavage.
  • Blastocyst — with holoblastic, partially unequal, asynchronous cleavage in mammals.
How to memorize

To remember the type of human cleavage, use the acronym HUA: Holoblastic, Unequal, Asynchronous.

Class and exam questions

Why does the total volume of the embryo not increase during cleavage?

A dense fertilization membrane persists around the embryo, which physically constrains growth and blocks the uptake of substances from the outside. The cells simply divide the existing volume of cytoplasm, becoming progressively smaller.

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

The reserves of the egg cell itself serve as building material. 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 fully functional independent organism.

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What else to study on this topic

  • Structure and functions of the fertilization envelope prior to implantation
  • Molecular mechanisms of differentiation into embryoblast and trophoblast
  • The process of cavitation: how the blastocyst cavity specifically forms
  • Experimental methods for inducing pluripotency and totipotency

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