Zingerone supplementation stimulates germ cell proliferation, inhibits apoptosis and modulates autophagy and ferroptosis in the mice testis.

The aim of this study was to evaluate the effects of zingerone supplementation on testicular spermatogenesis by analyzing germ cell proliferation, cell survival, and antioxidant status in the testis of mice. Zingerone was administered orally in three doses: 10, 25, and 50 mg/kg for 35 days. An in vitro study was also performed on the testicular explants treated with 5 and 25 mg/mL dose of zingerone. The present study revealed that zingerone treatment significantly increased the sperm concentration and cell proliferation. Furthermore, the expression of active caspase-3, transferrin receptor, GPx4 and the levels of MDA and SOD were found to be decreasing, while the levels of catalase and the expression of Bcl-2, LAMP2, AR, ER-β were significantly increasing in the zingerone treated group. Thus, these findings suggest that zingerone supplementation might promote spermatogenesis by stimulating germ cell proliferation, cell survival, and, inhibiting apoptosis and oxidative stress. Furthermore, modulation of autophagy and ferroptosis might be involved in the recycling of cellular component due to elevated proliferation and survival of cell in the mice testis. However, further investigation would be required to unravel the zingerone mediated exact role of autophagy and ferroptosis.