Programming for Meiotic Competence in Mouse Male Germ Cells is Established at the Perinatal Precursor Stage of Development

Meiosis is a fundamental aspect of gametogenesis, but how and when the programming is established in germ cells during development is unknown. In the mammalian male germline, mitotic differentiating spermatogonia with the competence for meiotic divisions arise from an undifferentiated pool of spermatogonia that are descended from prospermatogonial precursors. Here we provide evidence from mouse models that suggests programming for meiotic competence is established much earlier in the developmental trajectory of spermatogonia than previously believed, likely at the prospermatogonial stage in fetal life. Conditional overexpression of the gene Id4 in prospermatogonia led to a block in meiotic progression of spermatocytes during postnatal spermatogenesis. In contrast, meiotic progression was found to proceed when Id4 was conditionally overexpressed beginning in postnatal spermatogonia. Moreover, conditional overexpression of Id4 in the female germline beginning at the fetal stage of development after oocytes have initiated meiosis did not disrupt their ability to progress postnatally. Collectively, these findings suggest that a new stage for where mechanistic insights into the origin of meiotic competence in the male germline should be explored. Moreover, the findings place further precedence on defining how outside exposures can disrupt programming at the earliest stages of male germ cell development that will manifest at advanced maturation stages and lead to genomic abnormalities.