Meiosis in Mammalian Oocytes
At the beginning of most animal life, fertilisation unifies the haploid genomes of an egg and a sperm to generate a genetically unique zygote. This union restores a diploid genome in the newly formed embryo. For this to work, the genomes of egg and sperm progenitor cells need to be reduced to a haploid state before fertilisation. This is achieved by two rounds of a specialised form of cell division called meiosis. Oocytes, progenitor cells of eggs, are kept in ovaries where they are maintained in prophase of meiosis I. At this stage, recombined homologous chromosomes are held together in a bivalent structure inside the nucleus (Figure 1). When meiosis I resumes, the nuclear envelope disassembles and a spindle machinery that is assembled from microtubules captures and aligns the liberated chromosomes at its centre. Next, the spindle asymmetrically relocates to the oocyte surface where the homologous chromosomes are segregated at anaphase I and half of them are eliminated into a very small cell termed polar body. The remaining chromosomes are captured and aligned by the second meiotic spindle. At this stage, the cell is called an egg and awaits fertilisation.
Figure 1. Spindle assembly and chromosome segregation in meiosis I. Inside the nucleus of a prophase-arrested oocyte reside recombined homologous chromosomes that are held together in a bivalent structure. Upon NEBD, chromosomes are aligned onto the meiotic spindle, which then migrates to the cell’s surface and eliminates half of them into a small polar body. Chromosome cartoons in the lower panel show the arrangement of homologous chromosomes in the 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’s 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 an egg is fertilised by a sperm, sister chromatids are segregated during anaphase II and half of them are eliminated into a second polar body. The newly formed cell, the zygote, now contains the haploid genomes of the egg and the sperm. Soon after fertilisation, pronuclei are formed around the egg and sperm DNA and migrate the parental genomes, which are doubled by DNA replication, to the centre of the zygote (Figure 2). There, the pronuclei breakdown, the first mitotic spindle assembles and equally segregates sister chromatids into two daughter cells. This marks the start of mitotic divisions of the developing embryo.
Figure 2. Chromosome segregation in meiosis II and embryo formation. Upon fertilisation, sister chromatids are segregated and half of them are eliminated into a polar body. In the zygote, the male and female pronuclei are formed and migrate to the cell’s centre. After pronuclear envelope breakdown, the first mitotic spindle of the embryo segregates sister chromatids and gives rise to a 2-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.
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