Spermatogenesis associated 22 is required for DNA repair and synapsis of homologous chromosomes in mouse germ cells

Abstract

Analysis of the N-ethyl-N-nitrosourea (ENU)-induced repro42 mutation previously identified spermatogenesis associated 22 (Spata22) as a gene required for meiotic progression and fertility in both male and female mice, but its specific contribution to the process was unclear. Here we report on a novel, null allele of Spata22 (Spata22Gt) and confirm its requirement for germ cell development. Similar to repro42 mutant mice, histological and mating analyses indicate that gametogenesis is profoundly affected in Spata22Gt/Gt males and females, resulting in infertility. Cytological examination confirms that germ cells do not progress beyond zygonema and meiotic arrest is linked to impairment of both synapsis and DNA repair. Analysis of SPATA22 distribution reveals that it localizes to foci associated with meiotic chromosomes during prophase I and that the number of foci peaks at zygonema; there are also more SPATA22 foci in oocytes than in spermatocytes. Furthermore, SPATA22 co-localizes with a number of proteins involved in meiotic recombination, including RAD51, DMC1 and MLH1, and is present until mid-pachynema, suggesting a role in resolution of recombination intermediates. In fact, SPATA22 co-localizes with MLH1 in more than 20% of foci at pachynema. Analysis of Spata22Gt/Gt meiocytes confirms that SPATA22 is required for localization of MEIOB but not RPA, two proteins known to interact with SPATA22, and immunoblotting corroborates that production of MEIOB is indeed decreased in the absence of SPATA22. Together, these data suggest that SPATA22 is required for both meiotic recombination and synapsis during meiosis in mice.

Full-length transcriptome sequencing and comparative transcriptomic analysis to uncover genes involved in early gametogenesis in the gonads of Amur sturgeon (Acipenser schrenckii)

“…ATRX protein was present in adult human and rat testis and was expressed in spermatogonia, early meiotic spermatocytes and somatic cells [51]. Many members of spermatogenesis associated protein family genes (Sap) are identified in testes and play important roles in the spermatogenesis process in vertebrates including fish, for example, Sap2 [52,53], Sap4 [54], Sap6 [55], Sap22 [56], and so on. In our study, above mentioned genes were also identified to be sex-significant expression genes in testes, which suggest they may paly conserved role in the early spermatogenesis of sturgeon.…”

MEIOB and SPATA22 resemble RPA subunits and interact with the RPA complex to promote meiotic recombination

“…In mice, the absence of MEIOB induces an arrest at a zygotene/pachytene-like stage with an accumulation of unrepaired DSBs (19,26). Several lines of evidence suggest that during meiosis, MEIOB forms a complex with SPATA22, a meiosis-specific factor with unknown function (26)(27)(28)(29). Moreover, MEIOB and SPATA22 have been shown to interact with and colocalize with RPA subunits; the role and mode of these interactions remain to be understood (19,26,29).…”

Full-length transcriptome sequencing and comparative transcriptomic analysis to uncover genes involved in early gametogenesis in the gonads of Amur sturgeon (Acipenser schrenckii)

“…ATRX protein was present in adult human and rat testis and was expressed in spermatogonia, early meiotic spermatocytes and somatic cells [51]. Many members of spermatogenesis associated protein family genes (Sap) are identified in testes and play important roles in the spermatogenesis process in vertebrates including fish, for example, Sap2 [52,53], Sap4 [54], Sap6 [55], Sap22 [56], and so on. In our study, above mentioned genes were also identified to be sex-significant expression genes in testes, which suggest they may paly conserved role in the early spermatogenesis of sturgeon.…”