2. Academic Validation
  3. The impact of tetrachlorobisphenol A exposure during puberty: Altered Leydig cell development and induced endoplasmic reticulum stress in male mice

The impact of tetrachlorobisphenol A exposure during puberty: Altered Leydig cell development and induced endoplasmic reticulum stress in male mice

  • Ecotoxicol Environ Saf. 2023 Dec 29:270:115895. doi: 10.1016/j.ecoenv.2023.115895.
Zhiang Yao 1,  Shanhui Tao 1,  Yingji Lai 2,  Yang Yu 3,  Hong Wang 3,  Jianmin Sang 3,  Jin Yang 3,  Huitao Li 3,  Xiaoheng Li 3,  Yang Li 1,  Yangyang Ning 1,  Ren-Shan Ge 4,  Shijun Li 5
Affiliations

Affiliations

  • 1 Institute of Life Sciences, College of Life and Environmental Sciences，Wenzhou University, Wenzhou, Zhejiang 325000, China.
  • 2 Alberta Institute, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China.
  • 3 Key Laboratory of Structural Malformations in Children of Zhejiang Province, Key Laboratory of Wenzhou, 325000 Zhejiang Province, China; Department of Anaesthesiology and Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
  • 4 Key Laboratory of Structural Malformations in Children of Zhejiang Province, Key Laboratory of Wenzhou, 325000 Zhejiang Province, China; Department of Anaesthesiology and Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China. Electronic address: [email protected].
  • 5 Institute of Life Sciences, College of Life and Environmental Sciences，Wenzhou University, Wenzhou, Zhejiang 325000, China. Electronic address: [email protected].
PMID: 38159341 DOI: 10.1016/j.ecoenv.2023.115895
Abstract

Tetrachlorobisphenol A (TCBPA), a halogenated flame retardant and endocrine disruptor, has been detected in human urine and serum. While previous research has shown its impact on the reproductive system, investigations into its mechanisms during puberty remain limited. This study aims to explore the effects of TCBPA on Leydig cells in adolescent mice and potential underlying mechanisms. Male C57 mice of age 28 days were gavaged with 50, 100, and 200 mg/kg/day for 28 days. TCBPA did not alter body weight and testis weight but lowered testosterone levels at 100 and 200 mg/kg and reduced sperm count in the epididymis at 200 mg/kg. TCBPA lowered Leydig cell number at 200 mg/kg while it downregulated key Leydig cell gene (Lhcgr, Scarb1, Cyp11a1, Cyp17a1, Hsd3b6, Hsd17b3 and Insl3) as low as 50 mg/kg. Further study indicated that TCBPA induced Reactive Oxygen Species and caused endoplasmic reticulum stress. In vitro study in TM3 mouse Leydig cells showed that TCBPA indeed induced Reactive Oxygen Species and caused endoplasmic reticulum stress at 75 μM and inhibited testosterone production at this concentration and addition of antioxidant tocopherol can reverse it. These discoveries provide new insights and references for a deeper understanding of the toxic mechanisms of TCBPA on Leydig cells during puberty.

Keywords

Apoptosis; Endoplasmic reticulum stress; Leydig cell; Puberty; Tetrachlorobisphenol A.

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