Germline 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 Forkhead 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. Our results suggested that Foxj2 overexpression in the germ cells of mouse testes affects chaperone-mediated autophagy by upregulating LAMP2A, leading to spermatogenesis failure at the initiation of meiosis, thus resulting in male infertility. Our findings provide new insight into the function of FOXJ2 in spermatogenesis and the significance of autophagy regulation in spermatogenesis.