Bisphenol A: A Multi-modal Endocrine Disruptor
Chapter 6: A Novel Model for the Estrogenic Action of BPA in Developing Brain Following Maternal Ingestion
Published:04 Jan 2022
Special Collection: 2022 ebook collectionSeries: Issues in Toxicology
C. K. Wagner and A. Fahrenkopf, in Bisphenol A: A Multi-modal Endocrine Disruptor, ed. N. R. Gassman, The Royal Society of Chemistry, 2022, ch. 6, pp. 139-152.
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Bisphenol A (BPA) is an environmental endocrine disruptor with estrogenic effects. Despite growing evidence that exposure to BPA during development alters brain function and behavior, the mechanisms by which BPA exerts its effects in the developing brain are not well understood. Progesterone receptor (PR) expression in the medial preoptic nucleus (MPN) of perinatal rats is specifically dependent on the action of estradiol at estrogen receptor α (ERα). This specificity provides an innovative and sensitive model system to examine the estrogenic, ERα-dependent actions of BPA in developing brain following maternal ingestion. We review findings demonstrating that maternal ingestion of low, but not higher, doses of BPA increased PR expression in the MPN of fetal females, suggesting a disruption of the normal sexual differentiation process. Administration of BPA to female neonates also induced PR expression in the MPN, but this effect was completely abolished with the concomitant administration of an ER antagonist. We propose this model as a means to study the effects of BPA on the development of sex differences in brain and behavior and as a sensitive “bioassay” for the ERα-dependent actions of BPA actions, as well as those of BPA analogs such as bisphenol F and bisphenol S.