Effects of Perinatal Administration of Bisphenol A on the Neuronal Nitric Oxide Synthase Expressing System in the Hypothalamus and Limbic System of CD1 Mice

Abstract

Bisphenol A (BPA) is a well-known plastic-derived pollutant that can bind to oestrogen receptors and is considered an endocrine-disrupting chemical. Its impact on different behaviours in rodents has been largely investigated, however, only a few data are available on its effects upon neural circuits. In the present study, we investigated the long-term effects of early exposure of mice of both sexes to BPA on the nitrinergic system, one of the neural systems involved in the control of sexual behaviour and under the control of gonadal hormones. Mice of both sexes were exposed for eight prenatal and eight postnatal days to BPA that was administered to the mothers. The maternally-exposed mice were sacrificed at the age of 2 months and their brains were sectioned and immunohistochemically treated for the detection of neuronal nitric oxide synthase (nNOS). Significant effects of BPA exposure were detected for the number of immunoreactive cells in the medial preoptic nucleus and in the ventromedial subdivision of the bed nucleus of the stria terminalis, in a sex-oriented and dose-dependent way. These results indicate that BPA has a powerful effect on specific portions of the nNOS-immunoreactive system belonging to the accessory olfactory system that are particularly important for the control of sexual behaviour. In addition, they confirm that perinatal exposure to endocrine-disrupting chemicals, in particular to BPA, may have a high impact on the organisation of specific neural pathways that can later affect complex behaviours and functions.