Prenatal Exposure to an EDC Mixture, NeuroMix: Effects on Brain, Behavior, and Stress Responsiveness in Rats.

Andrea C Gore,Tatum Moore,Lindsay M Thompson,Matthew J Groom

doi:10.3390/toxics10030122

Andrea C Gore, Tatum Moore + Show 2 more

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https://doi.org/10.3390/toxics10030122

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Journal: Toxics	Publication Date: Mar 3, 2022
Citations: 9	License type: CC BY 4.0

Affiliation: The University of Texas at Austin

Abstract

Humans and wildlife are exposed to endocrine-disrupting chemicals (EDCs) throughout their lives. Environmental EDCs are implicated in a range of diseases/disorders with developmental origins, including neurodevelopment and behavior. EDCs are most often studied one by one; here, we assessed outcomes induced by a mixture designed to represent the real-world situation of multiple simultaneous exposures. The choice of EDCs, which we refer to as “NeuroMix,” was informed by evidence for neurobiological effects in single-compound studies and included bisphenols, phthalates, vinclozolin, and perfluorinated, polybrominated, and polychlorinated compounds. Pregnant Sprague Dawley rats were fed the NeuroMix or vehicle, and then offspring of both sexes were assessed for effects on postnatal development and behaviors and gene expression in the brain in adulthood. In order to determine whether early-life EDCs predisposed to subsequent vulnerability to postnatal life challenges, a subset of rats were also given a stress challenge in adolescence. Prenatal NeuroMix exposure decreased body weight and delayed puberty in males but not females. In adulthood, NeuroMix caused changes in anxiety-like, social, and mate preference behaviors only in females. Effects of stress were predominantly observed in males. Several interactions of NeuroMix and stress were found, especially for the mate preference behavior and gene expression in the brain. These findings provide novel insights into how two realistic environmental challenges lead to developmental and neurobehavioral deficits, both alone and in combination, in a sex-specific manner.

Highlights

Accepted: 26 February 2022An increasing number of endocrine-disrupting chemicals (EDCs) are associated with neurodevelopmental disorders
A growing body of evidence from animal studies, human epidemiology, and bioA growing body of evidence from animal studies, human epidemiology, and biomonimonitoring has demonstrated that environmental chemical mixtures represent the realtoring has demonstrated that environmental chemical mixtures represent the real-world world situation in wildlife and humans and that chemicals in combination may have efsituation in wildlife and humans and that chemicals in combination may have effects that fects that may not be predictable from single compounds [23,26,27,30,61,62]
Studies on low-dose mixtures of EDCs represent a new frontier in the field as they reveal how combinations of these chemicals may allow them to cause adverse effects below their no observed adverse effect level (NOAEL)

Summary

Introduction

Accepted: 26 February 2022An increasing number of endocrine-disrupting chemicals (EDCs) are associated with neurodevelopmental disorders. Specific to anxiety-like disorders, these relationships have been shown, to date, for bisphenol A (BPA) [15–18], phthalates such as DEHP [19,20], and persistent organic pollutants such as polychlorinated biphenyls (PCBs) [21,22] in both rodent and human studies. Beyond this “one chemical at a time” approach is growing evidence that mixtures of EDCs may have effects that cannot be predicted from outcomes based on single chemical testing. This means that doses of EDCs below the estimated no observed adverse effect level (NOAEL) for an endpoint may have adverse effects when given in combination [23–29]

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