OBJECTIVESThis paper aims to investigate the uterotrophic activities of lactational exposure to combination of soy isoflavones (SIF) and bisphenol A (BPA) and to examine estrogen receptor α (ERα) and estrogen receptor β (ERβ) expressions in hypothalamus-pituitary-ovary axis and uterus.

METHODSMaternal rats that were breeding about 8 litters were randomly divided into four groups with seven dams in each group. Dams in different treatment groups received corn oil (control), 150 mg/kg BW of SIF, 150 mg/kg BW of BPA or combination of 150 mg/kg BW of SIF and 150 mg/kg BW of BPA, respectively, from postnatal day 5 to 11 (PND5-11) by gavage. On PND12 and PND70, 10 female litters were killed and hypothalamus, pituitary, ovary and uterus were collected. ERα and ERβ expressions in these organs were detected with Western blotting assay. And vaginal opening time and estrus cycle were examined in animals fed for PND70.

RESULTSOn PND12, the relative uterine weight of rats treated with ISF or BPA or their combination was significantly higher than that of untreated rats (P<0.05). But the relative uterine weight of rats in the co-exposure group was slightly lower than that in the group only exposed to SIF or BPA. On PND 70, however, the relative uterine weight in each treatment group was not statistically different from that in the control group (P>0.05). Vaginal opening time and estrus cycle in groups treated with SIF or BPA or their combination were similar to those in the control group (P>0.05). Exposure to SIF or BPA or their combination could up-regulate or down-regulate ERα and ERβ expressions in hypothalamus, pituitary, ovary and uterus on PND12 and PND70. These regulation patterns for ERα and ERβ were different in different organs at different time points.

CONCLUSIONLactational exposure to ISF or BPA or their combination could induce uterotrophic responses in neonate rats, which disappeared in later life. But these data fail to suggest a possibility for synergic actions between SIF and BPA. It was also demonstrated that the uterotrophic effects of SIF and BPA exposure might, at least, involve modification of ERα or ERβ expressions in the hypothalamus-pituitary-ovary axis.

Animals ; Animals, Newborn ; Benzhydryl Compounds ; Blotting, Western ; Down-Regulation ; Drug Synergism ; Estrogen Receptor alpha ; biosynthesis ; Estrogen Receptor beta ; biosynthesis ; Estrogens, Non-Steroidal ; pharmacokinetics ; toxicity ; Female ; Hypothalamo-Hypophyseal System ; drug effects ; metabolism ; Isoflavones ; isolation & purification ; pharmacokinetics ; toxicity ; Lactation ; metabolism ; Maternal Exposure ; Organ Size ; drug effects ; Ovary ; drug effects ; metabolism ; Phenols ; pharmacokinetics ; toxicity ; Phytoestrogens ; isolation & purification ; pharmacokinetics ; toxicity ; Rats ; Rats, Sprague-Dawley ; Sexual Maturation ; drug effects ; Soybeans ; chemistry ; Up-Regulation ; Uterus ; drug effects ; metabolism