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母体接触 3-甲基胆蒽扰乱了 F1 代小鼠的肠肝循环。

Parental exposure 3-methylcholanthrene disturbed the enterohepatic circulation in F1 generation of mice.

机构信息

College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, 310032, Zhejiang, China.

College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, 310032, Zhejiang, China.

出版信息

Chemosphere. 2022 Jan;286(Pt 1):131681. doi: 10.1016/j.chemosphere.2021.131681. Epub 2021 Jul 26.

DOI:10.1016/j.chemosphere.2021.131681
PMID:34346331
Abstract

3-methylcholanthrene (3 MC) is an environmental compound belonging to the PAHs and is reportedly thought to be a risk factor for the prevalence of hepatic function disorder. Here, a dose of 0.5 mg/kg of 3 MC was given to 4-week-old male and female mice (F0) in their diet for 6 weeks. After exposure, then the mice were mated between different groups. The first filial (F1) generation offspring of exposed or unexposed parental mice were sacrificed at the age of 5 weeks (F1-5 W), and the potential effects on the F0 and F1 offspring were evaluated. The results showed that the total bile acids (TBAs) in the serum and feces in F0 females and female F1-5 W individuals born from female mice exposed to 3 MC decreased, while the TBAs in the liver increased. The transcriptional levels of major genes participating in synthesis, regulation, transportation and apical uptake was also altered correspondingly. In addition, the transcription of some genes related to inflammation was enhanced in these mice. Further investigation revealed that in addition to distinct changes in the mucus secretion, tight junction proteins and ion transport were induced, and antimicrobial peptides were also disrupted in the intestine of F0 mice and F1-5 W female offspring of maternal mice exposed to 3 MC. Our results suggested that exposure to 3 MC, but not male exposure, had the potential to interfere with BAs metabolism, affecting gut barrier function. Females were more seriously affected than males.

摘要

3-甲基胆蒽(3MC)是一种环境化合物,属于多环芳烃,据报道被认为是肝功能紊乱流行的一个风险因素。在这里,将 0.5mg/kg 的 3MC 剂量给予 4 周龄雄性和雌性小鼠(F0)的饮食中,持续 6 周。暴露后,然后将不同组别的小鼠进行交配。暴露或未暴露于父母鼠的第一代(F1)后代在 5 周龄(F1-5W)时被处死,并评估对 F0 和 F1 后代的潜在影响。结果表明,暴露于 3MC 的雌性 F0 血清和粪便中的总胆汁酸(TBAs)以及来自雌性小鼠的雌性 F1-5W 个体中的总胆汁酸减少,而肝脏中的 TBAs 增加。参与合成、调节、转运和顶端摄取的主要基因的转录水平也相应改变。此外,这些小鼠中一些与炎症相关的基因的转录增强。进一步的研究表明,除了粘液分泌的明显变化外,紧密连接蛋白和离子转运也被诱导,并且在暴露于 3MC 的 F0 小鼠和母鼠暴露的 F1-5W 雌性后代的肠道中抗菌肽也被破坏。我们的结果表明,暴露于 3MC(而非雄性暴露)有可能干扰 BAs 代谢,影响肠道屏障功能。雌性比雄性受影响更严重。

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