Yiwen Zhang, Jiabao Feng, Tongde Xie, Xinyue Zhang, Daian Pan, Shichao Liu, Daqing Zhao, Siming Wang, Meichen Liu, Shiting Yu
These findings indicate that CYCSE attenuates male reproductive aging, at least in part, through activation of testicular autophagy mediated by the mTOR-Beclin-1 pathway in Leydig and Sertoli cells. This study provides experimental evidence supporting the traditional application of Chinese yam in promoting male reproductive health.
ETHNOPHARMACOLOGICAL RELEVANCE: Dioscorea polystachya Turcz. (Chinese yam) is a Traditional Chinese Medicine with a documented history of over 2000 years for nourishing kidney essence and supporting male reproductive health. Despite its broad ethnomedical applications, it has not been comprehensively studied for its efficacy in delaying reproductive aging.
AIM OF THE STUDY: This study aimed to investigate the efficacy and underlying mechanisms of Chinese yam in attenuating aging-related reproductive decline.
MATERIALS AND METHODS: The protective effects of Chinese yam protein extract (CYCSE) were evaluated using a naturally aged rat model and D-galactose-induced senescent mouse Leydig (TM3) and Sertoli (TM4) cells. The mechanisms were investigated through histopathology, flow cytometry, transmission electron microscopy (TEM), Western blot, and pharmacological intervention assays.
RESULTS: In aged rats, CYCSE intervention ameliorated testicular histopathology, restored sperm parameters, and increased testosterone levels. In senescent TM3 and TM4 cells, CYCSE enhanced cell viability, suppressed apoptosis, and restored mitochondrial membrane potential. Furthermore, CYCSE up-regulated the expression of steroidogenic genes (Star, Cyp11a1) and spermatogenesis-related factors (Gdnf, Kitl, Bmp4), while reducing senescence markers (SA-β-gal activity, p16, p21, p53) and mitigating oxidative stress in both in vivo and in vitro models. TEM analysis confirmed that CYCSE restored autophagic flux in senescent TM3 and TM4 cells. Mechanistically, CYCSE restored impaired autophagic activity, which was associated with modulation of the mTOR-Beclin-1 signaling axis. The protective effects of CYCSE were substantially diminished by co-treatment with an mTOR activator, suggesting the involvement of this pathway.
CONCLUSIONS: These findings indicate that CYCSE attenuates male reproductive aging, at least in part, through activation of testicular autophagy mediated by the mTOR-Beclin-1 pathway in Leydig and Sertoli cells. This study provides experimental evidence supporting the traditional application of Chinese yam in promoting male reproductive health.