Icariin Ameliorates Spermatogenesis Disorder in Obese Mice Induced by High‐Fat Diet through Regulating the Glycolytic Pathway

Scope Obesity is a global threat for male infertility, which can cause spermatogenic dysfunction. However, there are no available drugs for the treatment of obesity‐induced spermatogenesis dysfunction. This study characterizes the protective effects of icariin (ICA) on spermatogenesis dysfunction in obese mice. Methods and results Obese mice are induced by a high‐fat diet to determine whether ICA has a protective effect. ICA treatment reduces body weight and the proportion of abnormal sperm, brings about a recovery of sperm count, and the number of spermatogenic cells. ICA treatment improves histopathological changes of the testes and inhibits testicular apoptosis, as evidenced by reduced the expression of Bax and increased the expression of Bcl‐2, PCNA, WT1, GATA‐4, vimentin, HK2, PKM2, and LDHA in the testes. In vitro, TM4 cells are treated with 0.4 mm palmitic acid (PA) to induce Sertoli cell injury, and are then utilized for ICA treatment. ICA improves PA‐induced decreased TM4 cells viability, reduces the levels of lactate, and increases the levels of pyruvate and the expression of HK2, PKM2, and LDHA and restores the glycolytic process in vitro. Conclusion ICA ameliorates spermatogenic dysfunction in obese mice by regulating glycolytic activity, providing effective strategies for obesity treatment. Two studies using obese mice and TM4 cells are carried out to evaluate if ICA can improve spermatogenic dysfunction in obese mice by modulating glycolytic activity. ICA reduces the expression of Bax, and increases that of PCNA, Bcl‐2, GATA‐4, WT1, vimentin, LDHA, PKM2, and HK2, which reveal that ICA can ameliorate spermatogenic dysfunction in obese mice by restoring glycolytic activity.