Protracted Impairment of Maternal Metabolic Health in Mouse Dams Following Pregnancy Exposure to a Mixture of Low Dose Endocrine-Disrupting Chemicals, a Pilot Study.

Alyssa K Merrill,Marissa Sobolewski,Deborah A Cory-Slechta,Tamarra James-Todd,Katherine Conrad,Elena Marvin,Timothy Anderson

doi:10.3390/toxics9120346

Alyssa K Merrill, Marissa Sobolewski + Show 5 more

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https://doi.org/10.3390/toxics9120346

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Journal: Toxics	Publication Date: Dec 9, 2021
Citations: 7	License type: CC BY 4.0

Affiliation: University of Rochester, Harvard University

Abstract

Pregnancy, a period of increased metabolic demands coordinated by fluctuating steroid hormones, is an understudied critical window of disease susceptibility for later-life maternal metabolic health. Epidemiological studies have identified associations between exposures to various endocrine-disrupting chemicals (EDCs) with an increased risk for metabolic syndrome, obesity, and diabetes. Whether such adverse outcomes would be heightened by concurrent exposures to multiple EDCs during pregnancy, consistent with the reality that human exposures are to EDC mixtures, was examined in the current pilot study. Mouse dams were orally exposed to relatively low doses of four EDCs: (atrazine (10 mg/kg), bisphenol-A (50 µg/kg), perfluorooctanoic acid (0.1 mg/kg), 2,3,7,8-tetrachlorodibenzo-p-dioxin (0.036 µg/kg)), or the combination (MIX), from gestational day 7 until birth or for an equivalent 12 days in non-pregnant females. Glucose intolerance, serum lipids, weight, and visceral adiposity were assessed six months later. MIX-exposed dams exhibited hyperglycemia with a persistent elevation in blood glucose two hours after glucose administration in a glucose tolerance test, whereas no such effects were observed in MIX-exposed non-pregnant females. Correspondingly, MIX dams showed elevated serum low-density lipoprotein (LDL). There were no statistically significant differences in weight or visceral adipose; MIX dams showed an average visceral adipose volume to body volume ratio of 0.09, while the vehicle dams had an average ratio of 0.07. Collectively, these findings provide biological plausibility for the epidemiological associations observed between EDC exposures during pregnancy and subsequent maternal metabolic dyshomeostasis, and proof of concept data that highlight the importance of considering complex EDC mixtures based of off common health outcomes, e.g., for increased risk for later-life maternal metabolic effects following pregnancy.

Highlights

Toxicological research has studied maternal exposures to understand the health of the fetus but has ignored the long-term health of the mother [1], despite the fact that pregnancy represents a unique critical window for later-life maternal metabolic health due to the unique metabolic demands of supporting fetal development [2,3]
Understanding the influence of endocrine-disrupting chemicals (EDCs) exposures during pregnancy on later-life maternal metabolic health is critical, as worldwide, approximately 1 in 10 women are living with a form of diabetes [29], a quantity expected to double in the decade [30]
Pregnancy is an understudied window of vulnerability for later-life maternal health [1,84], as the metabolic demands necessary for supporting fetal development may enhance maternal metabolic disease risk [2,3,85,86]

Summary

Introduction

Toxicological research has studied maternal exposures to understand the health of the fetus but has ignored the long-term health of the mother [1], despite the fact that pregnancy represents a unique critical window for later-life maternal metabolic health due to the unique metabolic demands of supporting fetal development [2,3]. Recent epidemiological studies have reported associations between EDC exposures, such as persistent organic pollutants, per and poly-fluoroalkyl substances, and bisphenols, during pregnancy and an increased risk of maternal hyperglycemia and gestational diabetes [10,11,12,13,14,15,16,17,18,19,20]. Epidemiological studies have found per and poly-fluoroalkyl substances and phthalates exposure during pregnancy to be associated with increased postpartum maternal adiposity [23,24]. Little remains known about the protracted impact of EDC exposures during pregnancy on later-life maternal metabolic health, including type 2 diabetes risk. Understanding the influence of EDC exposures during pregnancy on later-life maternal metabolic health is critical, as worldwide, approximately 1 in 10 women are living with a form of diabetes [29], a quantity expected to double in the decade [30]

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