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

  • Andrology. 2024 Apr 19. doi: 10.1111/andr.13645.
Guoqiang Liu  1 ,  Di Liu  1 ,  Minggang Zhu  1 ,  Mingrui Zhang  1 ,  Chunyang Li  2 ,  Xiaohong Xu  2 ,  Feng Pan  1
Affiliations
  • 1. Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
  • 2. Department of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Key Laboratory of, Ministry of Education for Neurological Disorders, Wuhan, Hubei, China.
PMID: 38639009 DOI: 10.1111/andr.13645
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.

Keywords
IGF‐1; apoptosis; high‐fat diet; obesity; proliferation; spermatogenesis.
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