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.
Endocrinology Department, Yancheng First Hospital, Affiliated Hospital of Nanjing University Medical School; The First people's Hospital of Yancheng, Yancheng, Jiangsu 224001, China.
Ecotoxicol Environ Saf. 2023 Jan 15;250:114497. doi: 10.1016/j.ecoenv.2023.114497. Epub 2023 Jan 4.
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.
先前的研究表明，氟调聚物醇（FTOH）会导致大鼠的肾毒性、肝毒性、亚慢性发育毒性和生殖毒性。然而，胚胎暴露于 6:2 FTOH 对后代小鼠生殖系统的影响尚不清楚。本研究旨在探讨胚胎暴露于 6:2 FTOH 对雄性后代小鼠生殖系统的生殖毒性作用及其相关分子机制。因此，从妊娠第 12.5 天到第 21.5 天，通过灌胃给予怀孕的老鼠玉米油或 6:2 FTOH。结果表明，胚胎暴露于 6:2 FTOH 会导致睾丸结构破坏，睾丸支持细胞（SCs）之间的紧密连接蛋白表达降低，血睾屏障（BTB）形成和成熟受损，精子活力降低，畸形增加，并在小鼠后代中引发睾丸炎症。进一步的体外研究表明，6:2 FTOH 通过激活 AKT/NF-κB 信号通路上调 MMP-8 的表达，进而增强occludin 的切割，导致SCs 屏障完整性破坏。综上所述，本研究表明，6:2 FTOH 暴露通过破坏 BTB 导致雄性后代生殖功能障碍，为 6:2 FTOH 暴露对后代的影响提供了新的见解。
