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  3. Protective effects of melatonin on DEHP-induced apoptosis and oxidative stress in prepubertal testes via the PI3K/AKT pathway

Protective effects of melatonin on DEHP-induced apoptosis and oxidative stress in prepubertal testes via the PI3K/AKT pathway

  • Environ Toxicol. 2023 Nov 17. doi: 10.1002/tox.24029.
Jiadong Chen 1 2 3 4 5,  Tianxin Zhao 6,  Xiangqin Zheng 1 2 3 4 5,  Lian Kang 1 2 3 4 5,  Junke Wang 1 2 3 4 5,  Yuexin Wei 1 2 3 4 5,  Yuhao Wu 1 2 3 4 5,  Lianju Shen 1 2 3 4 5,  Chunlan Long 1 2 3 4 5,  Guanghui Wei 1 2 3 4 5 7,  Shengde Wu 1 2 3 4 5 7
Affiliations

Affiliations

  • 1 Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Chongqing, China.
  • 2 Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China.
  • 3 National Clinical Research Center for Child Health and Disorders, Chongqing, China.
  • 4 China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing, China.
  • 5 Chongqing Key Laboratory of Pediatrics Chongqing, Chongqing, China.
  • 6 Department of Pediatric Urology, Guangzhou Woman and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
  • 7 Department of Urology, Children's Hospital of Chongqing Medical University, Chongqing, China.
PMID: 37975621 DOI: 10.1002/tox.24029
Abstract

Di(2-ethylhexyl) phthalate (DEHP), an environmental endocrine disruptor, is one of the most common plasticizers and is widely used in various plastic products. DEHP induces Apoptosis and oxidative stress and has been shown to have androgenic toxicity. However, the methods to combat DEHP-induced testicular damage and the mechanisms involved remain to be elucidated. In the present study, we used melatonin, which has strong antioxidant properties, to intervene in prepubertal mice and mouse Leydig cells (TM3) treated with DEHP or its metabolite mono(2-ethylhexyl) phthalate (MEHP). The results showed that melatonin protected against DEHP-induced testicular damage in prepubertal mice, mainly by protecting against DEHP-induced structural destruction of the germinal tubules and by attenuating the DEHP-induced decrease in testicular organ coefficients and testosterone levels. Transcriptomic analysis found that melatonin may attenuate DEHP-induced oxidative stress and Apoptosis in prepubertal testes. In vitro studies further revealed that MEHP induces oxidative stress injury and increases Apoptosis in TM3 cells, while melatonin reversed this damage. In vitro studies also found that MEHP exposure inhibited the expression levels of molecules related to the PI3K/Akt signaling pathway, and melatonin reversed this change. In conclusion, these findings suggest that melatonin protects against DEHP-induced prepubertal testicular injury via the PI3K/Akt signaling pathway, and provide a theoretical basis and experimental rationale for combating male reproductive dysfunction.

Keywords

PI3K/AKT signaling pathway; apoptosis; di(2-ethylhexyl) phthalate; melatonin; oxidative stress; prepubertal testes.

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