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.
- 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: [email protected].
- 6. Institute of Advanced Synthesis, School of Chemistry and Molecular Engineering, Nanjing Tech University, Nanjing, Jiangsu 211816, China. Electronic address: [email protected].
- 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: [email protected].
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.