%0 Journal Article
%T Insulin-like growth factor-1 promotes the testicular sperm production by improving germ cell survival and proliferation in high-fat diet-treated male mice.
%A Liu G
%A Liu D
%A Zhu M
%A Zhang M
%A Li C
%A Xu X
%A Pan F
%J Andrology
%V 0
%N 0
%D 2024 Apr 19
%M 38639009
%F 4.456
%R 10.1111/andr.13645
%X <B>BACKGROUND: </B>A 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.<BR><B>OBJECTIVE: </B>To investigate the therapeutic effect and potential mechanism of IGF-1 on spermatogenesis of high-fat diet (HFD)-induced obesity mice.<BR><B>METHODS: </B>An 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.<BR><B>RESULTS: </B>The 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.<BR><B>CONCLUSIONS: </B>Insufficient 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.