TOPAZ1, a germ cell specific factor, is essential for male meiotic progression.

Topaz1 (Testis and Ovary-specific PAZ domain gene 1) is a germ cell specific gene highly conserved in vertebrates. The putative protein TOPAZ1 contains a PAZ domain, specifically found in PIWI, Argonaute and Zwille proteins. Consequently, Topaz1 is supposed to have a role during gametogenesis and may be involved in the piRNA pathway and contribute to silencing of transposable elements and maintenance of genome integrity. Here we report Topaz1 inactivation in mouse. Female fertility was not affected, but male sterility appeared exclusively in homozygous mutants in accordance with the high expression of Topaz1 in male germ cells. Pachytene Topaz1--deficient spermatocytes progress through meiosis without either derepression of retrotransposons or MSCI dysfunction, but become arrested before the post-meiotic round spermatid stage with extensive apoptosis. Consequently, an absence of spermatids and spermatozoa was observed in Topaz1(-/-) testis. Histological analysis also revealed that disturbances of spermatogenesis take place between post natal days 15 and 20, during the first wave of male meiosis and before the generation of haploid germ cells. Transcriptomic analysis at these two stages showed that TOPAZ1 influences the expression of one hundred transcripts, most of which are up-regulated in mutant testis at post natal day 20. Our results also showed that 10% of these transcripts are long non-coding RNA. This suggests that a highly regulated balance of lncRNAs seems to be essential during spermatogenesis for induction of appropriate male gamete production.