Cleavage of Human Embryos: Options and Diversity

Abstract

In order to estimate the diversity of embryo cleavage relatives to embryo progress (blastocyst formation), time-lapse imaging data of preimplantation human embryo development were used. This retrospective study is focused on the topographic features and time parameters of the cleavages, with particular emphasis on the lengths of cleavage cycles and the genealogy of blastomeres in 2- to 8-cell human embryos. We have found that all 4-cell human embryos have four developmental variants that are based on the sequence of appearance and orientation of cleavage planes during embryo cleavage from 2 to 4 blastomeres. Each variant of cleavage shows a strong correlation with further developmental dynamics of the embryos (different cleavage cycle characteristics as well as lengths of blastomere cycles). An analysis of the sequence of human blastomere divisions allowed us to postulate that the effects of zygotic determinants are eliminated as a result of cleavage, and that, thereafter, blastomeres acquire the ability of own syntheses, regulation, polarization, formation of functional contacts, and, finally, of specific differentiation. This data on the early development of human embryos obtained using noninvasive methods complements and extend our understanding of the embryogenesis of eutherian mammals and may be applied in the practice of reproductive technologies.

Keywords: blastomere genealogy; cleavage; human embryos; time-lapse analysis.

Fig. 1

Examples of sequential equatorial (EE), meridional (MM), and meridional followed by equatorial (ME) blastomere divisions and final configuration of a 4-cell embryo in relation to 4-cell embryo formation. Equatorial followed by meridional (EM) cleavage type (not shown) is different from ME cleavage type only in the order of division. The time after intracellular sperm injection (h:m) is indicated on the figure. Asterisk depicts the position of the second polar body

Fig. 2

Embryo cleavage trajectories for EE, MM, ME, and EM cleavage type embryos. The green, red, and yellow lines indicate embryos with high, low, and medium cleavage intensities, respectively. Dashed lines indicate average embryo cleavage trajectories for each significantly different cleavage intensity group. Solid lines with markers depict average trajectories for each embryo variant. Horizontal axes stand for the number of blastomeres. Vertical axes indicate the time after intracellular sperm injection (h)

Fig. 3

Blastomere genealogy in EE, MM, ME and EM embryos. The numbers at bifurcation points show the order of blastomere appearance (same for every genealogy schemes). The lowest number stands for the shortest cycle length. Vertical axes indicate the time after intracellular sperm injection (h). Z – zygote

Fig. 4

Distribution of blastomere cleavage periods for 4-cell (left diagrams) and 8-cell (right diagrams) aggregates of MM, ME, and EM embryos. Horizontal axes depict the order of successive cellular divisions. Columns of various colors represent the division frequencies of each blastomere in relation to total cell divisions (in %, vertical axes) at a set moment of sequential division. The color code of blastomeres of different origins is presented in the legend in the upper right corner of the diagram