Stra8 and its inducer, retinoic acid, regulate meiotic initiation in both spermatogenesis and oogenesis in mice

Abstract

In eukaryotes, diploid cells give rise to haploid cells via meiosis, a program of two cell divisions preceded by one round of DNA replication. Although key molecular components of the meiotic apparatus are highly conserved among eukaryotes, the mechanisms responsible for initiating the meiotic program have diverged substantially among eukaryotes. This raises a related question in animals with two distinct sexes: Within a given species, are similar or different mechanisms of meiotic initiation used in the male and female germ lines? In mammals, this question is underscored by dramatic differences in the timing of meiotic initiation in males and females. Stra8 is a vertebrate-specific, cytoplasmic factor expressed by germ cells in response to retinoic acid. We previously demonstrated that Stra8 gene function is required for meiotic initiation in mouse embryonic ovaries. Here we report that, on an inbred C57BL/6 genetic background, the same factor is also required for meiotic initiation in germ cells of juvenile mouse testes. In juvenile C57BL/6 males lacking Stra8 gene function, the early mitotic development of germ cells appears to be undisturbed. However, these cells then fail to undergo the morphological changes that define meiotic prophase, and they do not display the molecular hallmarks of meiotic chromosome cohesion, synapsis and recombination. We conclude that, in mice, Stra8 regulates meiotic initiation in both spermatogenesis and oogenesis. Taken together with previous observations, our present findings indicate that, in both the male and female germ lines, meiosis is initiated through retinoic acid induction of Stra8. meiosis ͉ spermatocyte

Isolation and cytogenetic characterization of zebrafish meiotic prophase I mutants

“…Recently, it has been reported that Stra8 (Stimulated by retinoic acid gene 8), a tetrapod-specific gene that encodes a cytoplasmic protein and whose expression is induced by retinoic acid, is required for meiotic initiation in both the male and female germ lines in mice (Anderson et al, 2008). The spermatocytes in Stra8-deficient C57BL/6 inbred mice shows meiotic arrest in the preleptotene stage, during which spo11 mRNA is dramatically reduced and the g-H2AX protein is absent (Anderson et al, 2008).…”

“…The spermatocytes in Stra8-deficient C57BL/6 inbred mice shows meiotic arrest in the preleptotene stage, during which spo11 mRNA is dramatically reduced and the g-H2AX protein is absent (Anderson et al, 2008). In addition, the Sycp3 protein, although present, fails to load onto the chromosomes in Stra8-deficient mice.…”

Downregulation of Col1a1 induces differentiation in mouse spermatogonia

“…Pcna is expressed in proliferating spermatogonia and spermatocytes, but not in non-proliferating spermatogonia or preleptotene spermatocyte. 24 Stra8 is a vertebrate-specific gene whose expression is crucial for initiation of meiosis in both male and female germ cells 25 and its overexpression is known to promote the in vitro differentiation of mouse embryonic stem cells into spermatozoa. 21,26 Our observations suggest that in response to Col1a1 suppression, the spermatogonial proliferation appeared to be suspended, while their differentiation was trigged.…”

Genetics of germ cell development

“…Meiotic entry in both sexes requires the HLH protein Stimulated by Retinoic Acid gene 8 (STRA8). 102,103 In females, Stra8 is expressed in germ cells in response to retinoic acid (RA) beginning at E12.5-13.5, and meiotic prophase begins soon afterward. 104 In prenatal males, the cytochrome P450 enzyme CYP26B1 degrades retinoic acid, preventing induction of Stra8.…”