Decoding the RNA Regulatory Network in Medaka (Oryzias latipes) Spermatogenesis: Insights from a Germ Cell...

Spermatogenesis is a sophisticated process coordinated by germ cells and the somatic microenvironment. Circular RNAs (circRNAs), key components of competitive endogenous RNA (ceRNA) networks, form intricate post-transcriptional regulatory systems by sequestering microRNAs (miRNAs). However, the specific functions of these networks in spermatogenesis, particularly regarding the cell-intrinsic regulatory programs of germ cells, remain poorly understood. To address this, we utilized a unique foxl3 mutant model in medaka (Oryzias latipes), in which XX female germ cells spontaneously transdifferentiate into functional sperm within the ovarian somatic environment. This model enables the functional enrichment of core spermatogenic programs largely independent of male-specific somatic cues. Through whole-transcriptome sequencing and bioinformatic analysis, we identified 58 key circRNAs, 27 core miRNAs, and 2965 mRNAs, and constructed a candidate ceRNA regulatory network mediated by six circRNAs. Under genetically consistent conditions, this study elucidated a putative ceRNA network directly involved in the germ cell-dominant initiation of spermatogenesis, suggesting an essential role of these networks in germ cell fate determination. These findings provide new insights into the regulatory mechanisms of teleost spermatogenesis and offer valuable molecular targets for advancing reproductive medicine and improving breeding efficiency in aquaculture.