Transfer of maternally injected endocrine disruptors through breast milk during lactation induces neonatal Calbindin-D9k in the rat model

Abstract

The uterus is a highly estrogen-responsive tissue, which can be measured through changes in CaBP-9k expression. In this study, we investigated the potential for estrogenic compounds 4-tert-octylphenol (OP), nonylphenol (NP), bisphenol A (BPA), diethylstilbestrol (DES) and 17beta-estradiol (E2) to be transferred through breast milk from dam to neonate during lactation using the induction of CaBP-9k in uterine tissue as a biomarker. Dams were treated with OP, NP and BPA, dissolved in corn oil, at doses of 200, 400 and 600 mg/kg body weight per day l for 5 days after delivery. Dams and neonates were euthanized after 24h. Treatment with these estrogenic compounds increased the expression of CaBP-9k mRNA in the maternal uterus, in a dose-dependent manner. All doses of estrogenic compounds resulted in an increase in CaBP-9k protein levels. These compounds have an estrogenic effect on the maternal uterus during the lactation period as shown by the induction of both CaBP-9k mRNA and protein. In the neonatal uterus, the expression of CaBP-9k mRNA and protein significantly increased with DES exposure. There was a significant increase in CaBP-9k mRNA in neonatal uterus when the dams were treated with high doses of estrogenic compounds, but protein levels of CaBP-9k were undetectable. Taken together, these findings suggest that maternally injected estrogenic compounds may be transferred to neonates through breast milk and thus affecting uterine function, as shown by the induction of CaBP-9k gene expression in the neonatal uterus.