Retinoic acid is dispensable for meiotic initiation but required for spermiogenesis in the mammalian testis

Retinoic acid (RA) is the proposed mammalian 'meiosis inducing substance'. However, evidence for this role comes from studies in the fetal ovary, where germ cell differentiation and meiotic initiation are temporally inseparable. In the postnatal testis, these events are separated by more than 1 week. Exploiting this difference, we discovered that, although RA is required for spermatogonial differentiation, it is dispensable for the subsequent initiation, progression and completion of meiosis. Indeed, in the absence of RA, the meiotic transcriptome program in both differentiating spermatogonia and spermatocytes entering meiosis was largely unaffected. Instead, transcripts encoding factors required during spermiogenesis were aberrant during preleptonema, and the subsequent spermatid morphogenesis program was disrupted such that no sperm were produced. Taken together, these data reveal a RA-independent model for male meiotic initiation.

Automated summary

Retinoic acid (RA) is proposed as the substance that induces meiosis in mammals, but the evidence for this role is based on studies in fetal ovaries where germ cell differentiation and meiotic initiation are inseparable. However, in postnatal testes, these events are separated by more than 1 week. This study found that while RA is necessary for spermatogonial differentiation, it is not essential for meiotic initiation, progression, and completion in the testis, indicating an independent model for male meiotic initiation.