2. Academic Validation
  3. Triclosan inhibits testosterone biosynthesis in adult rats via inducing m6A methylation-mediated autophagy

Triclosan inhibits testosterone biosynthesis in adult rats via inducing m6A methylation-mediated autophagy

  • Environ Int. 2024 Jun 18:190:108827. doi: 10.1016/j.envint.2024.108827.
Jianmin Sang 1,  Zhongyao Ji 1,  Huitao Li 1,  Hong Wang 1,  Hehua Quan 1,  Yang Yu 1,  Jingyun Yan 1,  Zhixiang Mao 1,  Yiyan Wang 2,  Linxi Li 3,  Ren-Shan Ge 4,  Han Lin 5
Affiliations

Affiliations

  • 1 Department of Anesthesiology and Perioperative Medicine, the Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
  • 2 Department of Anesthesiology and Perioperative Medicine, the Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; Key Laboratory of Pediatric Anesthesiology, Ministry of Education and Key Laboratory of Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
  • 3 Department of Anesthesiology and Perioperative Medicine, the Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China. Electronic address: lilinxi@wmu.edu.
  • 4 Department of Anesthesiology and Perioperative Medicine, the Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; Key Laboratory of Pediatric Anesthesiology, Ministry of Education and Key Laboratory of Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; Key Laboratory of Environment and Male Reproductive Medicine of Wenzhou and Key Laboratory of Structural Malformations in Children of Zhejiang Province and, Zhejiang Province, China. Electronic address: renshan_ge@wmu.edu.
  • 5 Department of Anesthesiology and Perioperative Medicine, the Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; Key Laboratory of Pediatric Anesthesiology, Ministry of Education and Key Laboratory of Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China. Electronic address: nanlinhannansh@qq.com.
PMID: 38908274 DOI: 10.1016/j.envint.2024.108827
Abstract

Triclosan is a potent Antibacterial compound widely used in everyday products. Whether triclosan affects Leydig cell function in adult male rats remains unknown. In this study, 0, 50, 100, or 200 mg/kg/day triclosan was gavaged to Sprague-Dawley male rats from 56 to 63 days postpartum. Triclosan significantly reduced serum testosterone levels at ≥ 50 mg/kg/day via downregulating the expression of Leydig cell gene Lhcgr, Scarb1, Star, Cyp11a1, Hsd3b1, CYP17A1, and Hsd17b3 and regulatory transcription factor Nr3c2 at 100-200 mg/kg. Further analysis showed that triclosan markedly increased Autophagy as shown by increasing LC3II and BECN1 and decreasing SQSTM1. The mRNA m6A modification analysis revealed that triclosan significantly downregulated Fto expression at 200 mg/kg while upregulating Ythdf1 expression at 100 and 200 mg/kg, leading to methylation of Becn1 mRNA as shown by MeRIP assay. Triclosan significantly inhibited testosterone output in rat R2C Leydig cells at ≥ 5 μM via downregulating Fto and upregulating Ythdf1. SiRNA Ythdf1 knockdown can reverse triclosan-mediated Mitophagy in R2C cells, thereby reversing the reduction of testosterone output. In summary, triclosan caused Becn1 m6A methylation by downregulating Fto and upregulating Ythdf1, which accelerated Becn1 translation, thus leading to the occurrence of Autophagy and the decrease of testosterone biosynthesis.

Keywords

Autophagy; Leydig cell function; Steroidogenesis; Triclosan; m6A methylation.

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