biostudies-literatureUnknown13(7)Bai FRSpermatogenesis is a complex biological process that produces haploid spermatozoa and requires precise regulation by many tissue-specific factors. In this study, we explored the role and mechanism of Fork head box J2 (FOXJ2, which is highly expressed in spermatocytes) in the regulation of spermatogenesis using a germline-specific conditional Foxj2 knock-in mouse model (Stra8-Cre; Foxj2 ^tg/tg mouse). Foxj2 overexpression in mouse testes led to spermatogenesis failure, which started at the initiation of meiosis, and resulted in male infertility. Lysosomes and autophagy-related genes were upregulated in Stra8-cre; Foxj2 ^tg/tg mouse testes and the number of autolysosomes in the spermatocytes in Stra8-cre; Foxj2 ^tg/tg mice was increased. Chromatin immunoprecipitCell death & disease665https://www.ebi.ac.uk/biostudies/studies/S-EPMC9338950biostudies-literatureGermline FOXJ2 overexpression causes male infertility via aberrant autophagy activation by LAMP2A upregulation.PMC9338950Wu JWQian WZCai CBai FRLv HHu YQJiang ZXWu YJWu QQfalseGermline FOXJ2 overexpression causes male infertility via aberrant autophagy activation by LAMP2A upregulation.Spermatogenesis is a complex biological process that produces haploid spermatozoa and requires precise regulation by many tissue-specific factors. In this study, we explored the role and mechanism of Fork head box J2 (FOXJ2, which is highly expressed in spermatocytes) in the regulation of spermatogenesis using a germline-specific conditional Foxj2 knock-in mouse model (Stra8-Cre; Foxj2 ^tg/tg mouse). Foxj2 overexpression in mouse testes led to spermatogenesis failure, which started at the initiation of meiosis, and resulted in male infertility. Lysosomes and autophagy-related genes were upregulated in Stra8-cre; Foxj2 ^tg/tg mouse testes and the number of autolysosomes in the spermatocytes in Stra8-cre; Foxj2 ^tg/tg mice was increased. Chromatin immunoprecipit2022-01-01T00:00:00Z2022 Jul2025-04-19T20:34:57.17Z2025-04-19T20:34:57.17ZS-EPMC93389503590806610.1038/s41419-022-05116-w