The Beginning of Meiosis in Mammalian Female Germ Cells: A Never-Ending Story of Intrinsic and Extrinsic Factors

Abstract

Meiosis is the unique division of germ cells resulting in the recombination of the maternal and paternal genomes and the production of haploid gametes. In mammals, it begins during the fetal life in females and during puberty in males. In both cases, entering meiosis requires a timely switch from the mitotic to the meiotic cell cycle and the transition from a potential pluripotent status to meiotic differentiation. Revealing the molecular mechanisms underlying these interrelated processes represents the essence in understanding the beginning of meiosis. Meiosis facilitates diversity across individuals and acts as a fundamental driver of evolution. Major differences between sexes and among species complicate the understanding of how meiosis begins. Basic meiotic research is further hindered by a current lack of meiotic cell lines. This has been recently partly overcome with the use of primordial-germ-cell-like cells (PGCLCs) generated from pluripotent stem cells. Much of what we know about this process depends on data from model organisms, namely, the mouse; in mice, the process, however, appears to differ in many aspects from that in humans. Identifying the mechanisms and molecules controlling germ cells to enter meiosis has represented and still represents a major challenge for reproductive medicine. In fact, the proper execution of meiosis is essential for fertility, for maintaining the integrity of the genome, and for ensuring the normal development of the offspring. The main clinical consequences of meiotic defects are infertility and, probably, increased susceptibility to some types of germ-cell tumors. In the present work, we report and discuss data mainly concerning the beginning of meiosis in mammalian female germ cells, referring to such process in males only when pertinent. After a brief account of this process in mice and humans and an historical chronicle of the major hypotheses and progress in this topic, the most recent results are reviewed and discussed.

Expression profiles of meiotic genes in male vs. female gonads and gametes: Insights into fertility issues

“…Germ cells undergo a series of mitotic and meiotic divisions, followed by a differentiation program to produce highly specialized haploid gametes that, at fertilization, fuse and give rise to a totipotent zygote, capable of generating all somatic lineages/tissues and the next-generation of gametes ( Larose et al, 2019 ; Farini and De Felici, 2022 ). The proper completion of meiosis is essential for fertility and for ensuring the normal development of the offspring ( Farini and De Felici, 2022 ).…”

“…Germ cells undergo a series of mitotic and meiotic divisions, followed by a differentiation program to produce highly specialized haploid gametes that, at fertilization, fuse and give rise to a totipotent zygote, capable of generating all somatic lineages/tissues and the next-generation of gametes ( Larose et al, 2019 ; Farini and De Felici, 2022 ). The proper completion of meiosis is essential for fertility and for ensuring the normal development of the offspring ( Farini and De Felici, 2022 ). Therefore, revealing the molecular mechanisms and pathways underlying this unique process is pivotal for understanding human reproduction and fertility, as well as helping to identify therapeutic and diagnostic targets ( Larose et al, 2019 ; Farini and De Felici, 2022 ).…”

“…The proper completion of meiosis is essential for fertility and for ensuring the normal development of the offspring ( Farini and De Felici, 2022 ). Therefore, revealing the molecular mechanisms and pathways underlying this unique process is pivotal for understanding human reproduction and fertility, as well as helping to identify therapeutic and diagnostic targets ( Larose et al, 2019 ; Farini and De Felici, 2022 ).…”

“…Both female and male germ cells undergo meiosis; however, the timing of meiosis and the quantity of gametes that are produced differs in males and females ( Farini and De Felici, 2022 ). In mammals, meiosis begins during fetal life in females and continues until menopause, whilst in males it begins at puberty and is maintained throughout life ( Farini and De Felici, 2022 ).…”

“…Both female and male germ cells undergo meiosis; however, the timing of meiosis and the quantity of gametes that are produced differs in males and females ( Farini and De Felici, 2022 ). In mammals, meiosis begins during fetal life in females and continues until menopause, whilst in males it begins at puberty and is maintained throughout life ( Farini and De Felici, 2022 ). Understanding the molecular mechanisms behind the differences in meiosis onset and progression in males and females may contribute to the elucidation of genes involved in conditions affecting human reproduction.…”