Insulin-like Growth Factor-1 Promotes the Testicular Sperm Production by Improving Germ Cell Survival and Proliferation in High-fat Diet-treated Male Mice

Overview

Journal Andrology

Specialties Reproductive Medicine
Urology

Date 2024 Apr 19

PMID 38639009

Authors

Guoqiang Liu

Di Liu

Minggang Zhu

Mingrui Zhang

Chunyang Li

Xiaohong Xu

Feng Pan

Affiliations

Soon will be listed here.

Abstract

Background: 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.

Objective: To investigate the therapeutic effect and potential mechanism of IGF-1 on spermatogenesis of high-fat diet (HFD)-induced obesity mice.

Methods: 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.

Results: 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.

Conclusions: 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.

Citing Articles

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

Liu G, Liu D, Zhu M, Zhang M, Li C, Xu X Andrology. 2024; 13(2):342-358.

PMID: 38639009 PMC: 11815545. DOI: 10.1111/andr.13645.

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