Neonatal exposure to bisphenol A modifies the abundance of estrogen receptor α transcripts with alternative 5′-untranslated regions in the female rat preoptic

The xenoestrogen bisphenol A (BPA) is commonly ingested by humans. We examined the effects of neonatal exposure to low versus high doses of BPA over the control of estrogen receptor alpha (ER alpha) expression in the preoptic area (POA) of prepubertal female rats. Pups received s.c. injections every 48 h of BPA (high dose, 20 mg/kg and low dose, 0-05 mg/kg) or diethylstilbestrol (DES, 0-02 mg/kg) from postnatal day (PND) I to PND7 and were killed at PND8 or PND21. Relative expression of ERa transcripts containing alternative 5 -untranslated regions OS, ON, 0, OT, and El in POA were evaluated by f RT-PCR. Methylation status of ER alpha promoters was determined by bisulfited DNA restriction analysis and ERa protein by immunohistochemistry. In PND8, the high mediated by the decreased expression of EIk-7-0 and Ek alpha-OT variants. In contrast, the low dose of BPA augmented total ER alpha mRNA by increasing the expression of the ER alpha-E1 variant. In PND21, both BPA doses increased total ERa mRNA by means of the augmented expression of ER alpha-O and ER alpha-OT variants. In PND21, the methylation status of the ER alpha promoters and the circulating levels of estradiol were similar in all experimental groups. At PND8 and PND21, DES and the high dose of BPA decreased, while the low dose of BPA increased ER alpha, protein in the POA. These findings show that neonatal BPA exposure alters the abundance of hypothalamic ERa transcript variants and protein in a dose-dependent manner.