Regulation of spermatogenesis by miR-375_1 via tuning the meiotic process in Chlamys farreri

Spermatogenesis is a highly complex and tightly regulated biological process. Differentiation of spermatogonia and initiation of meiosis are precisely controlled by a network of genes and regulatory factors. Among these, microRNAs (miRNAs), a class of small non-coding RNAs, play essential roles in modulating spermatogenesis. Our previous studies in the scallop Chlamys farreri revealed that miR-375_1 exhibits significant sex-biased expression during early gonadal differentiation, suggesting its potential involvement in germ cell development. However, the precise function and mechanistic role of miR-375_1 in spermatogenesis remain unclear. In this study, we demonstrate that testis-specific overexpression of miR-375_1 disrupts spermatogenesis, leading to meiotic arrest at the spermatocyte stage. Furthermore, we identified that the meiosis-specific cohesin gene SCP3 is a direct target of miR-375_1 through high-throughput sequencing and luciferase reporter assays, providing a mechanistic explanation for the spermatogenic defects observed in miR-375_1-overexpressing testes. Our findings highlighted the significant role of miR-375_1 in regulating meiotic progression during male germ cell development and uncovered a novel miR-375_1- SCP3 regulatory module in the miRNA-mediated control of spermatogenesis. This study advances our understanding of the molecular mechanisms underlying germ cell differentiation and may provide insights into reproductive disorders associated with meiotic dysfunction.