Cultured Cordyceps Sinensis Ameliorates Oligoasthenozoospermia by Enhancing Testosterone Production via Activation of SF-1-mediated Steroid Hormone Biosynthesis

(CCS) improves sperm quality in patients with oligoasthenozoospermia (OAS), but its mechanisms remain unclear. A cyclophosphamide (CTX)-induced OAS mice model was employed to evaluate the effects of CCS on hormone secretion, blood-testis barrier (BTB) integrity, testicular oxidative stress, and spermatogenic cell apoptosis. The steroidogenic factor-1 (SF-1)-mediated steroid hormone biosynthesis was further examined. Our results demonstrated that CCS elevated serum hormone levels, increased BTB-related protein expression, and inhibited spermatogenic cell apoptosis. Furthermore, CCS upregulated the protein expression of steroidogenic enzymes and SF-1 in testes. In vitro, CCS extract enhanced testosterone production and steroidogenic enzyme expression in CTX-injured TM3 cells, concomitant with the upregulation of SF-1. Moreover, SF-1 knockdown reversed the effect of CCS extract on testosterone production. In conclusion, CCS improves OAS by enhancing testosterone production primarily via activation of SF-1-mediated steroid hormone biosynthesis. The increased testosterone contributes to maintaining BTB integrity and inhibiting testicular cell apoptosis.