1. Academic Validation
  2. Roles of ferroptosis in type 1 diabetes induced spermatogenic dysfunction

Roles of ferroptosis in type 1 diabetes induced spermatogenic dysfunction

  • Free Radic Biol Med. 2024 Feb 16:S0891-5849(24)00080-7. doi: 10.1016/j.freeradbiomed.2024.02.006.
Yalei Cao 1 Zirun Jin 2 Yu Xi 1 Jianxing Cheng 1 Zishui Fang 2 Qiancheng Zhao 2 Jiaming Weng 1 Jun Zhu 2 Yanlin Tang 1 Zhe Zhang 3 Hui Jiang 4
Affiliations

Affiliations

  • 1 Department of Urology, Center for Reproductive Medicine, Peking University Third Hospital, Beijing, China.
  • 2 Department of Urology, Peking University First Hospital, Beijing, China; Institute of Urology, Peking University, Beijing, China; Department of andrology, Peking University First Hospital, Beijing, China.
  • 3 Department of Urology, Center for Reproductive Medicine, Peking University Third Hospital, Beijing, China. Electronic address: zhezhang@bjmu.edu.cn.
  • 4 Department of Urology, Center for Reproductive Medicine, Peking University Third Hospital, Beijing, China; Department of Urology, Peking University First Hospital, Beijing, China; Institute of Urology, Peking University, Beijing, China; Department of andrology, Peking University First Hospital, Beijing, China. Electronic address: jianghui@bjmu.edu.cn.
Abstract

Diabetes mellitus (DM) is a widespread Metabolic Disease presenting with various complications, including spermatogenic dysfunction. However, the underlying mechanisms are still unclear. Ferroptosis, a novel type of programmed cell death, is associated with much metabolic diseases. Here, we investigated the role of Ferroptosis in spermatogenic dysfunction of streptozotocin (STZ)-induced type 1 diabetic mice (diabetic mice), high glucose (HG)-treated GC-2 cells (HG cells) as well as testicular tissues of diabetic patients. We found an accumulation of iron, elevated malondialdehyde level and reduced glutathione level in the testis tissues of diabetic mice and HG cells. Histological examination showed a decrease in spermatogenic cells and spermatids within the seminiferous tubules as well as mitochondrial shrinkage in the testis tissues of diabetic mice. Ferrostatin-1 (Fer-1), the inhibitor of Ferroptosis, mitigated ferroptosis-associated iron overload, lipid peroxidation accumulation and spermatogenic dysfunction of diabetic mice. Furthermore, we observed a downregulation of GPX4, FTL and SLC7A11 in diabetic mice and HG cells. Fer-1 treatment and GPX4 overexpression counteracted the effects of HG on cell viability, Reactive Oxygen Species, lipid peroxidation and glutathione via inhibition of Ferroptosis. Moreover, we found an elevation of Ferroptosis in testicular tissues of diabetic patients. Taken together, our results identify the crucial role of Ferroptosis in diabetic spermatogenic dysfunction and Ferroptosis may be a promising therapeutic target to improve spermatogenesis in diabetic patients.

Keywords

Diabetic infertility; Ferroptosis; GPX4; Oxidative stress; Spermatogenic dysfunction.

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