Timing of entry of meiosis depends on a mark generated by DNA methyltransferase 3a in testis

Reprogramming of DNA methylation is an essential part of gametogenesis, and a role of two members of the DNA methyltransferase (Dnmt) family, Dnmt3a and Dnmt3L, has been recognized. In an attempt to elucidate the role of Dnmt3a, we analyzed the progression of spermatogenesis in Dnmt3a(-/-) homozygotes during the first 3 weeks of post-natal development. The emerging picture was markedly different from that recently reported for the Dnmt3L protein. In the Dnmt3a(-/-) testis, at the expected time of entry into meiosis (11-13 dpp), the number of spermatocytes was greatly reduced. They progressively accumulated during the following days, but at a slower rate than in the wild type. Once started, however, the pachytene stage was apparently completed with normal chromosome pairing and formation of the sex vesicle, and spermatogenesis further progressed with the appearance and the expression of round spermatid specific markers. Interestingly and unlike Dnmt3L(-/-) spermatocytes, Dnmt3a(-/-) germ cells showed only a minor reduction in the methylation of interspersed repetitive elements and retroposons. The Dnmt3a might thus generate a mark important for the initiation of male meiosis that is distinct from that created by Dnmt3L.