Gonad‐specific transcription factor spermatogenesis‐ and oogenesis‐specific helix‐loop‐helix transcription factor 1 (SOHLH1) plays a key role in the transcriptional regulation of the expression of differentiating spermatogonial genes. However, its role in spermatocytes (meiotic male germ cells) remains largely unknown. In this study, Sohlh1 knockout (KO) male mice displayed meiotic defects at the zygotene stage during spermatogenesis. Microarray analyses identified 66 upregulated genes and 139 downregulated genes in Sohlh1 KO testes compared with those in wild‐type testes at postnatal Day 7.5. Among many of the downregulated genes, Sycp1 and Sycp3, which encode synaptonemal complex proteins 1 and 3 (SYCP1 and SYCP3), respectively, were significantly reduced in Sohlh1 knockout mice. Transmission electron microscopy revealed no formation of the synaptonemal complex in Sohlh1 KO spermatocytes. Luciferase reporter and chromatin‐immunoprecipitation assays demonstrated that SOHLH1 enhanced the expression of the Sycp1 and Sycp3 genes by binding the −1276, −708, and −94 basepairs (bp) E‐boxes upstream of the Sycp1 promoter and the −64 and −43 bp E‐boxes upstream of the Sycp3 promoter. Our data suggest that SOHLH1 transcriptionally regulates the expression of many target genes critical for the meiotic phase of spermatogenesis.

Previous studies have reported that only primordial follicles and empty follicles can be found in 7.5 days postparturition (dpp) Sohlh1−/− mouse ovaries and females are infertility. There appears to be a defect in follicle development during the primordial‐to‐primary follicle transition in Sohlh1−/− mouse ovaries. However, detailed analyses of these phenomena have not been performed. In this study, we used Sohlh1−/− transgenic mice to explore the role of Sohlh1 in folliculogenesis. The results showed that only primordial follicles and empty follicles can be observed in Sohlh1−/− ovaries from 0.5 to 23.5 dpp. The expression of Foxo3 and FOXO3 was downregulated; nucleocytoplasmic shuttling of FOXO3 was normal in 7.5‐dpp Sohlh1+/+ but not Sohlh1−/− ovaries; and primordial follicle activation (PFA) was not observed in 7.5‐dpp Sohlh1−/− mice. The expression levels of KIT, AKT, and P308‐AKT were downregulated (p < 0.05), whereas that of P473‐AKT was not significantly changed (p > 0.05). The KIT/PI3K/AKT pathway was inhibited. Furthermore, we conducted a dual luciferase assay and chromatin immunoprecipitation. The results showed that SOHLH1 can upregulate the Kit gene by binding to the −3698 bp E‐box motif. The absence of Sohlh1 may affect PFA in mouse ovaries via downregulation of Kit and inhibition of the KIT/PI3K/AKT pathway.

Cover Caption: The cover image is based on the Research Article Primordial follicle activation is affected by the absence of Sohlh1 in mice by Gongqing Liu et al., DOI: https://doi.org/10.1002/mrd.23078.