Chen Yu-Kui, Lai Ming-Quan, Zhang Qin-Yao, Zhong Mei-Ting, Zhang Jin-Jin, Chen Ya-Qi, Guo Xiao-Fan, Wang Qi, Xie Xiao-Li
Department of Toxicology, School of Public Health, Southern Medical University (Guangdong Provincial Key Laboratory of Tropical Disease Research), No. 1838 North Guangzhou Road, 510515, Guangzhou, China.
Department of Forensic Pathology, School of Forensic Medicine, Southern Medical University, No. 1838 North Guangzhou Road, 510515, Guangzhou, China.
Environ Pollut. 2025 Oct 1;382:126749. doi: 10.1016/j.envpol.2025.126749. Epub 2025 Jul 1.
Ammonium perfluoro (2-methyl-3-oxahexanoate) (GenX) is one of short-chain alternatives of perfluorooctanoic acid (PFOA) and has emerged as persistent global environmental pollutant due to its resistance to degradation. Nonetheless, the effects and mechanisms of perinatal exposure to GenX or PFOA on both mothers and offspring enterohepatic system remain poorly understood. In this study, pregnant C57BL/6J mice were administered 1 mg/kg body weight (bw)/day of PFOA or 2 mg/kg bw/day of GenX until the fourth week postpartum, with or without an inulin intervention at 5 g/kg bw/day. The results indicated that GenX or PFOA exposure significantly induced liver injury, gut microbiota imbalance, and intestinal barrier damage in the dams, as well as caused liver function changes, increase in the intestinal permeability, and pyroptosis induction in the pups. Furthermore, inulin intervention mitigated intestinal toxicity in the pups by remodeling the gut microbiota composition in the dams and inhibiting the TLR4/NF-κB/NLRP3 inflammatory pathway in the pups. Taken together, this study elucidated that intestinal homeostasis imbalance induced by the perinatal GenX or PFOA exposure in the dams vertically mediated intestinal toxicity in the pups and highlighted the potential therapeutic role of inulin, contributing to a better understanding and management of environmental pollutant-induced health issue.
全氟（2-甲基-3-氧杂己酸）铵（GenX）是全氟辛酸（PFOA）的短链替代品之一，由于其抗降解性已成为一种持久性全球环境污染物。尽管如此，围产期暴露于GenX或PFOA对母亲和后代肠肝系统的影响及机制仍知之甚少。在本研究中，给怀孕的C57BL/6J小鼠每日腹腔注射1 mg/kg体重（bw）的PFOA或2 mg/kg bw的GenX，直至产后第四周，同时或不同时给予5 g/kg bw的菊粉干预。结果表明，暴露于GenX或PFOA会显著诱导母鼠肝损伤、肠道微生物群失衡和肠屏障损伤，同时导致幼崽肝功能改变、肠道通透性增加和细胞焦亡。此外，菊粉干预通过重塑母鼠肠道微生物群组成和抑制幼崽的TLR4/NF-κB/NLRP3炎症通路减轻了幼崽的肠道毒性。综上所述，本研究阐明了围产期母鼠暴露于GenX或PFOA所诱导的肠道稳态失衡会垂直介导幼崽的肠道毒性，并突出了菊粉的潜在治疗作用，有助于更好地理解和管理环境污染物引起的健康问题。
