1. Academic Validation
  2. Capsaicin alleviates DEHP-induced testicular dysfunction by suppressing oxidative stress in mice

Capsaicin alleviates DEHP-induced testicular dysfunction by suppressing oxidative stress in mice

  • Toxicol Appl Pharmacol. 2026 Jan:506:117655. doi: 10.1016/j.taap.2025.117655.
Yi Liu 1 Xu Yan 2 Yinwei Chen 3 Longjie Gu 4 Lei Jin 5
Affiliations

Affiliations

  • 1 Reproductive Medicine Center, Tongji Hospital, Tongji Medicine College, Huazhong University of Science and Technology, Wuhan 430030, China.
  • 2 Hubei Clinical Research Center for Reproductive Medicine, Shiyan 442000, Hubei Province, China; Shiyan Key Laboratory of Reproduction and Genetics (Renmin Hospital, Hubei University of Medicine), China.
  • 3 Reproductive Medicine Center, Tongji Hospital, Tongji Medicine College, Huazhong University of Science and Technology, Wuhan 430030, China; Hubei Clinical Research Center for Reproductive Medicine, Shiyan 442000, Hubei Province, China; Shiyan Key Laboratory of Reproduction and Genetics (Renmin Hospital, Hubei University of Medicine), China.
  • 4 Reproductive Medicine Center, Tongji Hospital, Tongji Medicine College, Huazhong University of Science and Technology, Wuhan 430030, China; Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
  • 5 Reproductive Medicine Center, Tongji Hospital, Tongji Medicine College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: [email protected].
Abstract

Di(2-ethylhexyl) phthalate (DEHP) is a widespread environmental endocrine disruptor known to impair testicular function. Capsaicin, the bioactive compound in chili peppers, has not been thoroughly explored for its protective effects against DEHP-induced testicular damage. In this study, male C57BL/6 mice were divided into control, DEHP-exposed (200 mg/kg/day orally for 6 weeks), and DEHP-exposed with varying doses of capsaicin (5, 10, and 20 mg/kg/day orally for 6 weeks). Leydig and Sertoli cells were cultured in vitro with DEHP or capsaicin (0, 25, 50, and 100 μM). Chronic DEHP exposure impaired testicular development, leading to morphological abnormalities and reduced sperm quality, which were largely restored by capsaicin treatment. Both in vivo and in vitro assays revealed that capsaicin modulated the Bax/BCL2 ratio and inhibited testicular Apoptosis. Additionally, capsaicin restored DEHP-induced suppression of testosterone biosynthesis in Leydig cells and maintained the integrity of the blood-testis barrier in Sertoli cells. Mechanistically, these protective effects were likely due to the antioxidant properties of capsaicin. In conclusion, our findings suggest that capsaicin may serve as a promising therapeutic agent for mitigating DEHP-induced testicular dysfunction, offering valuable insights for potential clinical applications.

Keywords

Capsaicin; DEHP; Leydig Cell; Oxidative Stress; Sertoli Cell; Testis.

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