The effects of bisphenol A on emotional behavior depend upon the timing of exposure, age and gender in mice

• Prenatal and postnatal exposure to a very low dose of BPA affects behavior later in life.
• Larger behavioral effects are due to postnatal rather than prenatal exposure.
• Females are more sensitive to the effects of prenatal and postnatal exposure to BPA.

Experimental evidence suggests that endocrine-disrupting chemicals (EDCs) can permanently disrupt the development of sexually dimorphic behaviors and the structure of sexually dimorphic areas of the brain. EDC exposure has different effects depending on diverse factors, such as the timing and dose of the exposure, the maternal environment and the individual's age and sex. Among EDCs, bisphenol A (BPA) is one of the most studied because of its extensive use, which ranges from dentistry to food/drink packaging. In the present study, we aimed to investigate the behavioral effects of developmental exposure to a low dose of BPA with respect to the timing of the exposure, maternal environment, sex and age at testing. Starting from the last week of pregnancy to the first postpartum week, dams spontaneously drank either corn oil (control group) or a solution containing BPA (10 μg/kg bw/day). At birth, the litters were cross-fostered to different dams to differentiate among the effects of pre- and postnatal exposure. Pre- and postnatally exposed offspring underwent three diverse experimental paradigms for anxiety-related behaviors: as juveniles, a novelty test and at adulthood, both the free exploratory open field and elevated plus maze tests. At both testing ages, pre- and postnatally exposed females showed evidence of increased anxiety and were less prone to explore a novel environment relative to the control females, showing a behavioral profile more similar to control males than females. In this study, the direction of the behavioral changes was affected similarly by the pre- and postnatal exposures, resulting in a disruption of these sexually dimorphic behaviors, although with a greater effect associated with postnatal exposure primarily in females. Our findings indicate that non-reproductive, sexually dimorphic behaviors are sensitive to endocrine disruption during critical developmental periods—particularly the highly critical early neonatal stage. Combined with previous research, our study provides further evidence of the potential risks that even low doses of EDCs may pose to humans, with fetuses and infants being highly vulnerable.