Retinoic Acid Is Sufficient for the In Vitro Induction of Mouse Spermatocytes

Abstract

SummaryMeiosis is the key step in gametogenesis. However, the mechanism of mammalian meiosis remains poorly understood due to the lack of an in vitro model. Here, we report that retinoic acid (RA) is sufficient for inducing leptotene/zygotene spermatocytes from cultured mouse spermatogonial stem cells. Multiple genes regulated by RA were identified by RNA sequencing. RA in combination with pup Sertoli cell co-culture resulted in a higher induction efficiency of 28%. Comparisons in the transcriptomic profiles of the induced spermatogenic cells and the isolated ones revealed the progressive induction of the germ cells. Using this model, we showed that Stra8, Agpat3, Fam57a, Wdr91, and Sox30 contributed to the proliferation and meiosis initiation differentially. In conclusion, we have efficiently generated spermatocytes using an RA/pup Sertoli cell-based in vitro model and provided proof-of-concept evidence for its application in identifying genes involved in mammalian meiosis.

Another piece of the meiosis puzzle

“…The simple observational techniques used to initially describe meiosis have in more recent times given way to mechanistic molecular, cellular and biochemical approaches. A good example of this is the recent report by Wang et al 1. which uses a new culture system to advance our understanding of mechanisms underlying retinoic acid (RA) effects on testicular meiosis and provides a novel experimental tool to facilitate future progress in this field.…”

“…A recent report by Wang et al 1. demonstrated that RA alone could induce meiosis and result in the production of leptotene/zygotene spermatocytes from cultured mouse SSCs.…”

“…The use of a monoculture of SSCs in the work of Wang et al 1. allowed specific gene expression in the SSCs during meiosis to be evaluated, something that was difficult in previous work where more than one cell type was used in the culture.…”

“…In summary, the development of a new serum-free culture system by Wang et al 1. in which RA alone is able to drive meiosis in pure cultures of mouse SSCs provides a new and powerful tool to explore the signaling events involved in the initiation and progression of meiosis.…”

“…Despite the importance of meiosis in spermatogenesis, our mechanistic knowledge of how this process worked has been relatively limited. The work of Wang et al 1. provides an important step forward in our efforts to understand exactly how meiosis is regulated, and the powerful new culture system for examining RA effects on meiosis will be an important tool for this group and others in future work to more clearly understand the mysteries of meiosis.…”