2. Academic Validation
  3. Role of ferroptosis mediated by abnormal membrane structure in DEHP-induced reproductive injury

Role of ferroptosis mediated by abnormal membrane structure in DEHP-induced reproductive injury

  • Free Radic Biol Med. 2025 Aug 1:235:150-161. doi: 10.1016/j.freeradbiomed.2025.04.026.
Wei Deng 1,  Jie Zhao 2,  Xia Wang 3,  Dinggang Li 4,  Mingxin Wang 5,  Xiangqin Zheng 6,  Runchang Wang 7,  Qitong Guo 8,  Peng Zhao 9,  Hao Yan 10,  Lianju Shen 11,  Chunlan Long 12,  Guanghui Wei 13,  Shengde Wu 14
Affiliations

Affiliations

  • 1 Department of Urology Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, 400014, Chongqing, China; Chongqing Key Laboratory of Structural Birth Defect and Reconstruction, Children Urogenital Development and Tissue Engineering of Chongqing Education Commission of China, 400014, Chongqing, China. Electronic address: 1341312656@qq.com.
  • 2 Department of Urology Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, 400014, Chongqing, China; Chongqing Key Laboratory of Structural Birth Defect and Reconstruction, Children Urogenital Development and Tissue Engineering of Chongqing Education Commission of China, 400014, Chongqing, China. Electronic address: 745259954@qq.com.
  • 3 Department of Urology Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, 400014, Chongqing, China; Chongqing Key Laboratory of Structural Birth Defect and Reconstruction, Children Urogenital Development and Tissue Engineering of Chongqing Education Commission of China, 400014, Chongqing, China; Hubei Enshi College, 445000, Hubei, China. Electronic address: 1573908733@qq.com.
  • 4 Department of Urology Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, 400014, Chongqing, China; Chongqing Key Laboratory of Structural Birth Defect and Reconstruction, Children Urogenital Development and Tissue Engineering of Chongqing Education Commission of China, 400014, Chongqing, China. Electronic address: ldg970824@gmail.com.
  • 5 Department of Urology Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, 400014, Chongqing, China; Chongqing Key Laboratory of Structural Birth Defect and Reconstruction, Children Urogenital Development and Tissue Engineering of Chongqing Education Commission of China, 400014, Chongqing, China. Electronic address: 2664629145@qq.com.
  • 6 Department of Urology Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, 400014, Chongqing, China; Chongqing Key Laboratory of Structural Birth Defect and Reconstruction, Children Urogenital Development and Tissue Engineering of Chongqing Education Commission of China, 400014, Chongqing, China. Electronic address: 1319148925@qq.com.
  • 7 Department of Urology Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, 400014, Chongqing, China; Chongqing Key Laboratory of Structural Birth Defect and Reconstruction, Children Urogenital Development and Tissue Engineering of Chongqing Education Commission of China, 400014, Chongqing, China. Electronic address: runchangwang@stu.cqmu.edu.cn.
  • 8 Department of Urology Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, 400014, Chongqing, China; Chongqing Key Laboratory of Structural Birth Defect and Reconstruction, Children Urogenital Development and Tissue Engineering of Chongqing Education Commission of China, 400014, Chongqing, China. Electronic address: 437910024@qq.com.
  • 9 Department of Urology Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, 400014, Chongqing, China; Chongqing Key Laboratory of Structural Birth Defect and Reconstruction, Children Urogenital Development and Tissue Engineering of Chongqing Education Commission of China, 400014, Chongqing, China. Electronic address: 251543148@qq.com.
  • 10 Department of Urology Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, 400014, Chongqing, China; Chongqing Key Laboratory of Structural Birth Defect and Reconstruction, Children Urogenital Development and Tissue Engineering of Chongqing Education Commission of China, 400014, Chongqing, China. Electronic address: yanhao17398977990@126.com.
  • 11 Department of Urology Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, 400014, Chongqing, China; Chongqing Key Laboratory of Structural Birth Defect and Reconstruction, Children Urogenital Development and Tissue Engineering of Chongqing Education Commission of China, 400014, Chongqing, China. Electronic address: 277190286@qq.com.
  • 12 Department of Urology Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, 400014, Chongqing, China; Chongqing Key Laboratory of Structural Birth Defect and Reconstruction, Children Urogenital Development and Tissue Engineering of Chongqing Education Commission of China, 400014, Chongqing, China. Electronic address: 332005363@qq.com.
  • 13 Department of Urology Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, 400014, Chongqing, China; Chongqing Key Laboratory of Structural Birth Defect and Reconstruction, Children Urogenital Development and Tissue Engineering of Chongqing Education Commission of China, 400014, Chongqing, China. Electronic address: u806806@cqmu.edu.cn.
  • 14 Department of Urology Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, 400014, Chongqing, China; Chongqing Key Laboratory of Structural Birth Defect and Reconstruction, Children Urogenital Development and Tissue Engineering of Chongqing Education Commission of China, 400014, Chongqing, China. Electronic address: shengdewu@hospital.cqmu.edu.cn.
PMID: 40306442 DOI: 10.1016/j.freeradbiomed.2025.04.026
Abstract

Di-(2-ethylhexyl) phthalate (DEHP), a commonly used plasticizer, has been demonstrated to possess reproductive toxicity; however, the precise mechanisms underlying this effect have yet to be fully elucidated. This study aimed to investigate the potential mechanisms by which prepubertal DEHP exposure impairs testicular development and to provide possible therapeutic targets. We exposed BALB/c male mice from postnatal days 22-35 to different doses of DEHP (0, 250, and 500 mg/kg/day) and utilized lipid metabolomics and Other methods to elucidate the reproductive damage caused by DEHP from a multidimensional tissue-cell-molecule perspective. Our findings indicate that DEHP exposure induces Ferroptosis in testicular tissue by remodeling membrane lipid structure, in which the imbalance of phospholipid-polyunsaturated fatty acids (PL-PUFA) and phospholipid-monounsaturated fatty acids (PL-MUFA) playing a crucial role. DEHP exposure altered the expression of ACSL4 and MBOAT2 via HIPPO and Androgen Receptor pathways, thereby impacting PL-PUFA/PL-MUFA synthesis. In conclusion, this study highlights a link between DEHP-induced reproductive damage and lipid metabolism reprogramming, suggesting new targets for preventing DEHP-induced reproductive toxicity.

Keywords

ACSL4; Di-(2-ethylhexyl) phthalate; Ferroptosis; MBOAT2; Reproduction.

Figures
Products
Inhibitors & Agonists