Insight Into the Molecular Program of Meiosis

Abstract

“We estimate that >2,300 genes (~4% of the mouse genome) are dedicated to male germ cellspecific transcripts, 99% of which are first expressed during or after meiosis”. This quotation from a paper published by Schultz et al. (2003), reflects the tremendous complexity of gamete production, the essence of which is meiosis. Meiosis is a differantiative process in which seemingly contradicting molecular pathways are activated simultaneously. On one hand the regular components and checkpoints of the cell division machinery, which is complex enough by itself, are utilized, but on the other hand a whole array of genes are activated to enable the unique characteristics of the meiotic division, such as partition of homologous chromosomes, and not the sister chromatides, in meiosis I, or executing cell division without a prior DNA duplication in meiosis II. On one hand double strand breaks are deliberately formed to ensure pairing of homologous chromosomes and recombination, but on the other hand a whole array of genes involved in DNA repair and safeguarding genome integrity are alerted. The meiotic complexity is also exemplified by the extensive dependence on a cross-talk between germ cells themselves, and between the differentiating germ cells and their surrounding somatic cells, i.e. Sertoli cells in the testis or granulosa cells in the ovarian follicle. Finally, the complexity of the meiotic process is depicted by the differences between males and females, regarding both the outcome of the meiotic division (four basically similar post meiotic round spermatids in the male versus one functional egg and three polar body cells that degenerate in the female), and its kinetics (a continuous process in the male versus an in-continuous process in the female). It is, therefore, absolutely crucial that the very many different molecular pathways operating during meiosis be tightly concerted and regulated. However, Virginia Hughes, in a paper published in Nature medicine (2008), stated that: “So far, scientists have identified nearly 300 DNA mutations in man with reproductive defects”, implying that our understanding of the meiotic molecular network is still very limited, although significant progress has been made since 2008.