Impact of Estrogen Withdrawal and Replacement in Female Mice along the Intestinal Tract. Comparison of E2 Replacement with the Effect of a Mixture of Low Dose Pollutants

Claudie Pinteur, Benoit Julien, Nathalie Véga, Hubert Vidal, Danielle Naville and Brigitte Le Magueresse-Battistoni
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Claudie Pinteur: Univ-Lyon, CarMeN Laboratory, INSERM U1060, INRAE U1397, Université Claude Bernard Lyon1, F-69310 Pierre-Bénite, France
Benoit Julien: Univ-Lyon, CarMeN Laboratory, INSERM U1060, INRAE U1397, Université Claude Bernard Lyon1, F-69310 Pierre-Bénite, France
Nathalie Véga: Univ-Lyon, CarMeN Laboratory, INSERM U1060, INRAE U1397, Université Claude Bernard Lyon1, F-69310 Pierre-Bénite, France
Hubert Vidal: Univ-Lyon, CarMeN Laboratory, INSERM U1060, INRAE U1397, Université Claude Bernard Lyon1, F-69310 Pierre-Bénite, France
Danielle Naville: Univ-Lyon, CarMeN Laboratory, INSERM U1060, INRAE U1397, Université Claude Bernard Lyon1, F-69310 Pierre-Bénite, France
Brigitte Le Magueresse-Battistoni: Univ-Lyon, CarMeN Laboratory, INSERM U1060, INRAE U1397, Université Claude Bernard Lyon1, F-69310 Pierre-Bénite, France

IJERPH, 2021, vol. 18, issue 16, 1-14

Abstract: 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.

Keywords: ovariectomy; estradiol replacement; gut-liver tissue axis; high-fat, high-sucrose diet; mixture of pollutants; metabolic disorders (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2021
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