由于荷尔蒙缺乏,绝经后妇女代表了对内分泌干扰物的脆弱人群。我们以前证明,长期暴露于卵巢切除的C57Bl6/J小鼠喂食高脂肪,高蔗糖饮食与一种二恶英的低剂量化学物质混合物,一个多氯联苯,一种邻苯二甲酸酯,和双酚A引发了肝脏的代谢改变,但没有探索肠道。然而,胃肠道是污染物进入人体的主要途径。在本研究中,我们调查了卵巢戒断和E2替代对各肠段的代谢后果,同时调查了污染物混合物的影响.我们表明,基因编码雌激素受体(Esr1,Gper1不是Esr2),异源加工基因(例如,Cyp3a11,Cyp2b10),和与空肠肠道稳态相关的基因(例如,Cd36,Got2,Mmp7)和肠道中胆汁酸的生物合成(例如,Fgf15、Slc10a2)和肝脏(例如,Abcb11,Slc10a1)受雌激素调节。暴露于污染物模仿了E2替代的一些影响,特别是在回肠(例如,Esr1,Nr1c1)表明该混合物具有雌激素模拟活性。本发现对于了解绝经后观察到的雌激素丢失情况,对雌激素依赖性代谢改变具有重要意义。
Postmenopausal women represent a vulnerable population towards endocrine disruptors due to hormonal deficit. We previously demonstrated that chronic exposure of ovariectomized C57Bl6/J mice fed a high-fat, high-sucrose diet to a low-dose mixture of chemicals with one dioxin, one polychlorobiphenyl, one phthalate, and bisphenol A triggered metabolic alterations in the liver but the intestine was not explored. Yet, the gastrointestinal tract is the main route by which pollutants enter the body. In the present study, we investigated the metabolic consequences of ovarian withdrawal and E2 replacement on the various gut segments along with investigating the impact of the mixture of pollutants. We showed that genes encoding estrogen receptors (Esr1, Gper1 not Esr2), xenobiotic processing genes (e.g., Cyp3a11, Cyp2b10), and genes related to gut homeostasis in the jejunum (e.g., Cd36, Got2, Mmp7) and to bile acid biosynthesis in the gut (e.g., Fgf15, Slc10a2) and liver (e.g., Abcb11, Slc10a1) were under estrogen regulation. Exposure to pollutants mimicked some of the effects of E2 replacement, particularly in the ileum (e.g., Esr1, Nr1c1) suggesting that the mixture had estrogen-mimetic activities. The present findings have important implications for the understanding of estrogen-dependent metabolic alterations with regards to situations of loss of estrogens as observed after menopause.