Autistic-like traits in Lewis rats exposed perinatally to a mixture of common endocrine disruptors

Abstract

Epidemiological data suggest that prenatal exposure to either phthalates or flame retardants can affect mental and motor development, and can provoke internalizing behavior and attention deficit. We hypothesize that simultaneous exposure in utero to several environmental endocrine disruptors such as phthalates and flame retardants at low doses impairs brain development and leads to behavioral traits similar to those observed in Autism Spectrum Disorders (ASD). To characterize behavior relevant to ASD and common co-morbidities such as ADHD (Attention Deficit Hyperactivity Disorder) rat offspring were exposed perinatally to a mixture of phthalates and flame retardants (DEHP, DBP, DiNP, BDE-47, BDE-99) at low doses. Pregnant Lewis rats were divided into 3 groups: negative control; exposed to the mixture of endocrine disruptors; and a positive control for ASD, valproic acid, an antiepileptic drug known to cause autism in humans. Following perinatal exposure by daily gavage, behavioral tests were administered to offspring: nest-seeking behavior, auditory startle reflex, open field, elevated plus maze, and a test of social interactions. Offspring exposed to the mixture of phthalates and PBDEs showed hyperactivity, and the males had lower maternal bonding and reduced social interactions. In addition, both males and females from the exposure group showed a remarkable escaping behavior, not present in the other groups. Exposure to low doses of phthalates and flame retardants provokes behavioral alterations consistent with certain autistic- and ADHD-like traits.