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Neurosci Res. 2003 Mar;45(3):345-56.

Low dose effects of bisphenol A on sexual differentiation of the brain and behavior in rats.

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  • 1Department of Integrative Physiology, Graduate School of Medical Sciences, Kyushu University, 812-8582, Fukuoka, Japan.


There is an endocrinological concern that environmental endocrine disrupters (EEDs) may influence sexual differentiation. Bisphenol A (BPA), one of EEDs, is released from polycarbonate plastics, and has been detected in the human umbilical cord. In this study, we examined the effect of BPA on the sexual differentiation of open-field behavior and the sexually dimorphic nuclei in the brain in the offspring of rats exposed to BPA during the fetal and suckling periods at a dosage below the human tolerable daily intake (TDI) level. In the control group, females were more active in the open field and had a larger locus coeruleus (LC) volume than males. BPA abolished and inverted the sex differences of the open-field behavior and the LC volume, respectively, without affecting the reproductive system. We also compared the effects of estrogenic compounds, diethylstilbestrol (DES) and resveratrol (RVT), to that of BPA because of their structural similarities. DES affected the open-field behavior, LC volume and reproductive system, while RVT affected the LC volume and the reproductive system. These results suggest that the brain is highly sensitive to BPA at a dosage below TDI and that the disrupting effects of BPA on sexual differentiation may vary from those of RVT and DES.

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