MEIOSIS EXPLAINED

Meiosis in Mammalian Oocytes

At the start of animal life, fertilization merges the haploid genomes of an egg and a sperm to form a genetically unique zygote. This restores diploidy in the embryo. To make this possible, the genomes of egg and sperm precursors must first be reduced to a haploid state through two rounds of a specialized division called meiosis.

Oocytes, the precursors of eggs, are stored in the ovary, arrested in prophase of meiosis I. Here, homologous chromosomes that have recombined are paired into bivalents within the nucleus (Figure 1). When meiosis I resumes, the nuclear envelope breaks down, and a spindle made of microtubules assembles to capture and align the chromosomes. The spindle then shifts asymmetrically to the oocyte surface, where homologous chromosomes separate at anaphase I, and half are discarded into a small polar body. The second meiotic spindle then organizes the remaining chromosomes. At this point, the cell is an egg, waiting for fertilization.

Figure 1. Spindle assembly and chromosome segregation in meiosis I. Inside the nucleus of a prophase-arrested oocyte, recombined homologous chromosomes are paired in a bivalent structure. After nuclear envelope breakdown (NEBD), chromosomes align on the meiotic spindle, which then migrates to the cell surface and expels half of them into a small polar body. Chromosome cartoons in the lower panel illustrate the arrangement of homologous chromosomes at different stages of meiosis I.

© Binyam Mogessie

You can watch below a movie of a mouse oocyte going through the fascinatingly complex process of meiosis I.

Movie 1. Spindle assembly and chromosome segregation in a mouse oocyte.
The meiotic spindle (grey) is assembled from microtubules after nuclear envelope breakdown (NEBD), followed by the alignment of chromosomes (magenta) at its equator. The spindle then relocates to the oocyte surface, where homologous chromosomes are segregated during anaphase I. The movie ends with the assembly of the second meiotic spindle in meiosis II. The egg is arrested in metaphase II at this stage and awaits fertilisation.

When a sperm fertilizes an egg, sister chromatids are separated during anaphase II, and half are discarded into the second polar body. The resulting zygote now contains the haploid genomes of both parents. Soon after fertilization, pronuclei form around the DNA of the egg and sperm, which then replicate and migrate to the center of the zygote (Figure 2). There, the pronuclei break down, the first mitotic spindle assembles, and sister chromatids are evenly segregated into two daughter cells. This marks the beginning of embryonic mitotic divisions.

Figure 2. Chromosome segregation in meiosis II and embryo formation. Upon fertilization, the sister chromatids are separated, and half of them are eliminated into a polar body. In the zygote, male and female pronuclei form and migrate to the center of the cell. After pronuclear envelope breakdown, the first mitotic spindle segregates sister chromatids and produces a two-cell embryo.

© Binyam Mogessie

Further Reading:

Dunkley S, Scheffler K, Mogessie B. Cytoskeletal form and function in mammalian oocytes and zygotes.
Curr Opin Cell Biol. 2022 Apr;75:102073.

Mogessie, B., Scheffler, K., and Schuh M. (2018). Assembly and Positioning of the Oocyte Meiotic Spindle.
Annu Rev Cell Dev Biol. 34:381-403.

Nagaoka, S.I., Hassold, T.J., and Hunt, P.A. (2012). Human aneuploidy: mechanisms and new insights into an age-old problem.
Nat Rev Genet 13, 493-504.

Unraveling the mysteries of female meiosis through quantitative cell biology