A deregulated expression of estrogen-target genes is associated with an altered response to estradiol in aged rats perinatally exposed to Bisphenol A

Abstract

Here we assessed the effects of perinatal exposure to bisphenol A (BPA) on the uterine response to 17bestradiol(E2) in aged rats. Pregnant rats were orally exposed to 0.5 or 50 mg BPA/kg/day from gestationalday 9 until weaning. On postnatal day (PND) 360, the rats were ovariectomized and treated with E2 forthree months. The uterine tissue of BPA50 and BPA0.5 rats showed increased density of glands withsquamous metaplasia (GSM) and glands with daughter glands respectively. Wnt7a expression was lowerin GSM of BPA50 rats than in controls. The expression of estrogen receptor 1 (ESR1) and its 50- untranslatedexons ESR1-O and ESR1-OT was lower in BPA50 rats. Both doses of BPA modified theexpression of coactivator proteins and epigenetic regulatory enzymes. Thus, perinatal BPA-exposed ratsshowed different glandular abnormalities associated with deregulated expression of E2-target genes.Different mechanisms would be involved depending on the BPA dose administered.