Maternal organophosphate flame-retardant exposure alters offspring feeding, locomotor and exploratory behaviors in a sexually-dimorphic manner in mice

Increased usage of organophosphate flame retardants (OPFRs) has led to detectable levels in pregnant women and neonates, which is associated with negative neurological outcomes. Therefore, we investigated if maternal OPFR exposure altered adult offspring feeding, locomotor, and anxiety-like behaviors on a low-fat (LFD) or high-fat diet (HFD). Wild-type C57Bl/6J dams were orally dosed with vehicle (sesame oil) or an OPFR mixture (1 mg/kg combination each of tris(1,3-dichloro-2-propyl)phosphate, triphenyl phosphate and tricresyl phosphate) from gestation day 7 to postnatal day 14. After weaning, pups were fed either a LFD or HFD until 19 weeks of age. Locomotor and anxiety-like behaviors were evaluated with the open field test, elevated plus maze, and metabolic cages. Feeding behaviors and meal patterns were analyzed by a Biological Data Acquisition System. Anogenital distance was reduced in OPFR-exposed male pups, but no effect was detected on adult body weight. We observed interactions of OPFR exposure and HFD consumption on locomotor and anxiety-like behavior in males, suggesting an anxiogenic effect while reducing overall nighttime activity. We also observed an interaction of OPFR exposure and HFD on weekly food intake and feeding behaviors. OPFR-exposed males consumed more total HFD than oil-exposed males during the 72-hour trial. However, when arcuate gene expression was analyzed, OPFR exposure induced Agrp expression in females, which would suggest greater orexigenic tone. Collectively, the implications of our study are that the behavioral effects of OPFR exposure are modulated by adult HFD consumption, which may influence the metabolic and neurological consequences of maternal OPFR exposure.