## 3 Results
Values are means \(\pm\) SEM with \(n\) = 6–8. **\(p\) < 0.01; *\(p\) < 0.05. Sham: Sham-operated mice. SAT as observed in the liver, while no significant effect was described in the VAT samples (Figure S2). It indicated that xenobiotic receptors were transcriptionally regulated in a distinct way depending on metabolic tissues. Impact of Estrogens and of the Pollutant Mixture on the Expression of Genes Related to Gut Homeostasis in the Jejunum  
Then, we investigated the expression of various nuclear receptors which have been shown to cross-interact with estrogen signaling machinery including Nr1i1 encoding the vitamin D receptor [30], the growth hormone receptor (GHR) [31], and Nr3c1 and Nr3c2, encoding the gluco- and mineralo-corticoid receptors, respectively [32]. With the exception of Nr3c2, all receptors had their mRNA expression levels significantly decreased in E2-replaced Ovx mice compared to Ovx mice, suggesting that estrogens exerted a negative regulation. Consistently, Ovx resulted in increased mRNA levels of Nr1i1. Exposure to pollutants only affected Nr3c1 mRNA levels by decreasing mRNA levels as observed with E2 replacement (Figure 3). Figure 3: Effect of ovariectomy alone (Ovx) or with 17\(\beta\)-estradiol (E2) supplementation (Ovx+E2) or with exposure to pollutants (Ovx + Poll) on the expression of genes encoding various nuclear receptors, lipid and glucose transporters, and mucin 2 and MMP7 in the jejunum. Values are means \(\pm\) SEM with \(n=6\)–8. *** \(p<0.001\); ** \(p<0.01\); ** \(p<0.05\). Sham: Sham-operated mice. Figure 2: Effect of ovariectomy alone (Ovx) or with 17\(\beta\)-estradiol (E2) supplementation (Ovx+E2) or with exposure to pollutants (Ovx + Poll) on the expression of genes encoding xenobiotic processing genes including the xenobiotic receptors (AHR, PXR, and CAR) and the CYP3A11 and CYP2B10 in the jejunum (**A**); the CYP3A11 and CYP2B10 in the ileum (**B**) and the colon (**C**). Values are means \(\pm\) SEM with \(n=6\)–8. *** \(p<0.001\); ** \(p<0.01\); * \(p<0.05\). Sham: Sham-operated mice. It has been suggested that estrogens can alter the expression of genes encoding inflammatory markers, as well as those related to intestinal permeability thus impacting gut homeostasis [33]. To determine the regulatory roles of estrogens in the different intestinal segments, genes encoding different important metabolic genes were also analyzed by RT-qPCR. The jejunum is a major site for nutrient uptake but only genes involved in fatty acid uptake, as evidenced by measurements of mRNA levels of Cd36 and Got2 (encoding the fatty acid binding protein mFABP), was subject to estrogen regulation. Indeed, ovariectomy resulted in an increase in Cd36 levels, which was completely avoided in Ovx mice that received E2 supplementation. The data for Got2 were less significant and only a decreasing trend (\(p=0.06\)) was observed between the Ovx and Ovx+E2 replacement groups (Figure 3). In contrast, the expression of the glucose transporter (i.e., the solute carrier genes Slc2a2 and Slc5a1 encoding Glucose Transporter 2, GLUT2, and sodium-dependent glucose cotransporter SGLT1, respectively), the fructose transporter (Slc2a5 encoding GLUT5), and the cholesterol transporter (Npc11I gene encoding the Niemann Pick C1 Like-1, NPC1L1) genes was not altered (Figure 3). Mucin 2, which is an indicator of goblet cells and the metalloproteinase MMP7 that converts inactive pro-defensins synthesized by Paneth cells to active molecules mediating host defense and homeostasis at the intestinal mucosal surface [34] were explored, as well. When compared to Ovx mice, we found that Mmp7 mRNA levels were significantly increased in Ovx mice E2-replaced and Muc2 mRNA levels were enhanced in Ovx mice exposed to the mixture of pollutants (Figure 3). Impact of Estrogens and of the Pollutant Mixture on the Expression of Genes Related to Gut Homeostasis in the Ileum and Colon  
The various nuclear receptors quantified in the jejunum were also analyzed in the ileum and colon.