Adult Male Rats Show Resilience to Adolescent Bisphenol A Effects on Hormonal and Behavioral Responses While Co-Exposure With Hop Extracts Supports Synergistic Actions.

Alexandre Morin,Lise Van de Beeck,Helene Plamondon,Emmanuelle Person

doi:10.3389/ftox.2021.639820

Abstract

The adolescence period, marked by sexual and brain maturation, has shown sensitivity to various environmental disruptors. Exposure to the xenoestrogen bisphenol A (BPA) is known to alter physiological and behavioral responses although its role at this critical period remains largely unknown. Recent research further suggests biochemical and genomic effects of BPA to be mitigated by various natural compounds, while effects on behavior have not been examined. This study aimed to characterize (1) the effects of dietary BPA during adolescence on endogenous corticosterone (CORT) secretion, emotional behavior, and testosterone (T) in adulthood, and (2) the impact of combined exposure to BPA with hop extracts (Hop), a phytoestrogen with anxiolytic properties. To do so, four groups of male Wistar rats [postnatal day (PND) 28] were administered corn oil (control), BPA (40 mg/kg), hops (40 mg/kg), or BPA-hops by oral gavage for 21 days (PND 28–48). Blood droplets collected on PND 28, 48, and 71 served to measure CORT and T changes. As adults, rats were tested in the elevated plus maze (EPM), the social interaction test, and the forced swim test. Our findings demonstrated elevated anxiety and a trend toward depressive-like behaviors in BPA- compared to hops-exposed rats. However, BPA intake had no impact on basal CORT levels, or adulthood T secretion and sociability. Of note, BPA's anxiogenic effect manifested through decreased EPM open arm entries was abolished by hops co-supplementation. Together, our observations suggest the adolescence period to be less sensitive to deleterious effects of BPA than what has been reported upon gestational and perinatal exposure.

Highlights

Bisphenol A (BPA) is a pollutant used in the manufacturing of polycarbonate plastics and resins used in many food containers, toys, and dental equipment, whose presence is associated with food and water contamination
This study aimed to investigate the impact of 21-day dietary exposure to BPA and hops during adolescence on CORT secretion profile, and characterize delayed effects on anxiety, sociability, and T secretion in adulthood
We determined that BPA- and hopexposed rats differed in anxiety, with hops-exposed animals showing reduced anxiety

Summary

Introduction

Bisphenol A (BPA) is a pollutant used in the manufacturing of polycarbonate plastics and resins used in many food containers, toys, and dental equipment, whose presence is associated with food and water contamination. Dietary BPA exposure has been linked to long-term adverse health effects, including endocrine dysregulation (Fujiwara et al, 2016) In this context, upregulation of Adolescent Bisphenol A Exposure Effects basal and stress-induced corticosterone (CORT) levels has been observed following gestational and lactational low-dose BPA exposure (40 μg/kg/day) in male rats (Panagiotidou et al, 2014) while perinatal and adult low- and high-dose exposure increased anxiety and depressive-like behavior (Matsuda et al, 2012; Chen et al, 2014; Xu et al, 2015). Most research on BPA has been conducted in the perinatal setting, leaving a paucity of research addressing exposure to pharmacological doses during adolescence This stage is important to examine considering the likelihood for BPA’s effects to differ throughout the lifespan, and that adolescence plays a critical role in socioemotional and endocrine maturation

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