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  3. Embryonic 6:2 FTOH exposure causes reproductive toxicity by disrupting the formation of the blood-testis barrier in offspring mice

Embryonic 6:2 FTOH exposure causes reproductive toxicity by disrupting the formation of the blood-testis barrier in offspring mice

  • Ecotoxicol Environ Saf. 2023 Jan 4;250:114497. doi: 10.1016/j.ecoenv.2023.114497.
Yunhui Xia 1,  Lanxiang Hao 2,  Yueyang Li 3,  Yifan Li 4,  Junhan Chen 1,  Lei Li 2,  Xiaodong Han 1,  Yanmei Liu 5,  Xiaojian Wang 6,  Dongmei Li 7
Affiliations

Affiliations

  • 1 Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, Jiangsu 210093, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, Jiangsu 210093, China.
  • 2 Endocrinology Department, Yancheng First Hospital, Affiliated Hospital of Nanjing University Medical School; The First people's Hospital of Yancheng, Yancheng, Jiangsu 224001, China.
  • 3 Institute of Advanced Synthesis, School of Chemistry and Molecular Engineering, Nanjing Tech University, Nanjing, Jiangsu 211816, China.
  • 4 State Key Laboratory of Coordination Chemistry, Jiangsu Key Laboratory of Advanced Organic Materials, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, Jiangsu 210023, China.
  • 5 Endocrinology Department, Yancheng First Hospital, Affiliated Hospital of Nanjing University Medical School; The First people's Hospital of Yancheng, Yancheng, Jiangsu 224001, China. Electronic address: lym_jsyc@sina.com.
  • 6 Institute of Advanced Synthesis, School of Chemistry and Molecular Engineering, Nanjing Tech University, Nanjing, Jiangsu 211816, China. Electronic address: ias_xjwang@njtech.edu.cn.
  • 7 Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, Jiangsu 210093, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, Jiangsu 210093, China. Electronic address: lidm@nju.edu.cn.
PMID: 36608565 DOI: 10.1016/j.ecoenv.2023.114497
Abstract

Previous studies have revealed nephrotoxicity, hepatotoxicity, subchronic developmental and reproductive toxicity in rats exposed to fluorotelomer alcohol (FTOH). However, the effects of embryonic 6:2 FTOH exposure on the reproductive system of offspring mice remain unclear. The purpose of this study is to explore the reproductive toxic effects of embryonic 6:2 FTOH exposure on offspring male mice and the related molecular mechanisms. Therefore, the pregnant mice were given corn oil or 6:2 FTOH by gavage from gestational days 12.5-21.5. The results demonstrated that embryonic 6:2 FTOH exposure resulted in disrupted testicular structure, low expression of tight junction protein between Sertoli cells (SCs), impaired blood-testis barrier (BTB) formation and maturation, reduced sperm viability and increased malformation, and induced testicular inflammation in the offspring of mice. Further in vitro studies showed that 6:2 FTOH treatment upregulated MMP-8 expression by activating Akt/NF-κB signaling pathway, which in turn enhanced occludin cleavage leading to the disruption of SCs barrier integrity. In summary, this study demonstrated that 6:2 FTOH exposure caused reproductive dysfunction in male offspring through disruption of BTB, which provided new insights into the effects of 6:2 FTOH exposure on the offspring.

Keywords

6:2 fluorotelomer alcohol (6:2 FTOH) Sertoli cells Reproductive toxicity Inflammation.

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