circLDHC controls sertoli cell maturation and metabolic remodeling through the miR-370-AR axis

Sertoli cells (SCs) are crucial for testicular development, transitioning from a proliferative to a metabolically active state during puberty to facilitate germ-cell differentiation. However, the molecular switches governing this maturation remain unclear. Here, we identified a previously uncharacterized circular RNA, circLDHC, as a key regulator of SCs fate. Transcriptomic analysis and RT-qPCR validation showed that circLDHC expression increased during pubertal testicular development and was higher in mature than in immature SCs. In immature SCs, circLDHC overexpression reduced proliferative activity, accompanied by decreased expression of proliferation and cellcycle related genes and reduced S-phase entry. In peripubertal SCs, circLDHC increased the expression of AR and HSD17B4 and promoted lactate production and lipid droplet accumulation. Mechanistically, circLDHC acted as a competing endogenous RNA that sponged miR-370, thereby releasing androgen receptor (AR) from miRNA mediated repression. Dual-luciferase assays confirmed that miR-370 directly targets AR, and functional rescue assays supported the circLDHC/miR-370/AR axis. These findings reveal a circLDHC/miR-370/AR regulatory axis that coordinates SC proliferation arrest and metabolic maturation. This work provides new insights into the noncoding RNA mediated control of puberty onset in boars. It offers potential molecular targets for improving reproductive performance and understanding Sertoli cell dysfunction in mammals.