Neonatal exposure to bisphenol A (BPA) modifies the abundance of estrogen receptor alpha (ERa) transcripts with alternative 5’ unstranslated regions in the female rat preoptic area

MONJE LUCAS; VARAYOUD JORGELINA; LUQUE ENRIQUE H; RAMOS J GUILLERMO

JOURNAL OF ENDOCRINOLOGY

BIOSCIENTIFICA LTD

Lugar: Bristol; Año: 2007 vol. 194 p. 201 - 212

0022-0795

The xenoestrogen bisphenolA(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 a (ERa) 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) 1 to PND7 and were killed at PND8 or PND21. Relative expression of ERa transcripts containing alternative 50-untranslated regions OS, ON, O, OT, and E1 in POA were evaluated by RT-PCR. Methylation status of ERa promoters was determined by bisulfited DNA restriction analysis and ERa protein by immunohistochemistry. In PND8, the high dose of BPA and DES diminished total ERa mRNA levels,mediated by the decreased expression of ERa-O and ERa-OT variants. In contrast, the low dose of BPA augmented total ERa mRNA by increasing the expression of the ERa-E1 variant. In PND21, both BPA doses increased total ERa mRNAby means of the augmented expression of ERa-O and ERa-OT variants. In PND21, the methylation status of the ERa promoters and the circulating levels of estradiol were similar in all experimental groups. AtPND8and PND21, DES and the high dose of BPAdecreased, while the lowdose of BPA increased ERa 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.