Insulin‐like growth factor‐1 promotes the testicular sperm production by improving germ cell survival and proliferation in high‐fat diet‐treated male mice

Abstract

AbstractBackgroundA decrease in semen volume among men is comparable to the rising prevalence of obesity worldwide. The anabolic hormone insulin‐like growth factor‐1 (IGF‐1) can promote proliferation and differentiation in cultured mouse spermatogonial stem cells and alleviate abnormal in vitro spermatogenesis. Additionally, serum IGF‐1 level is negatively correlated with body mass index. Whereas the role of IGF‐1 in the sperm production in obese men remains unclear.ObjectiveTo investigate the therapeutic effect and potential mechanism of IGF‐1 on spermatogenesis of high‐fat diet (HFD)‐induced obesity mice.MethodsAn HFD‐induced obesity mouse model was established. Alterations in testicular morphology, sperm count, proliferation, and apoptosis were observed by H&E staining,immunohistochemistry, immunofluorescence, and Western blotting. Exogenous recombinant IGF‐1 was administered to obese mice to investigate the correlations between altered testicular IGF‐1 levels and sperm production.ResultsThe sperm count was reduced, the testicular structure was disordered, and sex hormone levels were abnormal in HFD‐fed mice compared with normal diet‐fed mice. The expression of proliferation‐related antigens such as proliferating cell nuclear antigen (PCNA) and Ki‐67 was decreased, while that of proapoptotic proteins such as c‐caspase3 was increased in testes from HFD‐fed mice. Most importantly, the phosphorylation of insulin‐like growth factor‐1 receptor (IGF‐1R) in testes was decreased due to reductions in IGF‐1 from hepatocytes and Sertoli cells. Recombinant IGF‐1 alleviated these functional impairments by promoting IGF‐1R, Akt, and Erk1/2 phosphorylation in the testes.ConclusionsInsufficient IGF‐1/IGF‐1R signaling is intimately linked to damaged sperm production in obese male mice. Exogenous IGF‐1 can improve survival and proliferation as well as sperm production. This study provides a novel theoretical basis and a target for the treatment of obese men with oligozoospermia.