Strain specific induction of pyometra and differences in immune responsiveness in mice exposed to 17α-ethinyl estradiol or the endocrine disrupting chemical bisphenol A

Abstract

Pyometra is an inflammatory disease of the uterus that can be caused by chronic exposure to estrogens. It is unknown whether weakly estrogenic endocrine disruptors can cause pyometra. We investigated whether dietary exposures to the estrogenic endocrine disruptor bisphenol A (BPA) induced pyometra. Pyometra did not occur in CD1 mice exposed to different dietary doses of BPA ranging from 4.1 to >4000μg/kg-d or 17α-ethinyl estradiol (EE; 1.2 to >150μg/kg-d). In the C57BL/6 strain, pyometra occurred in the 15μg/kg-d EE and 33μg/kg-d BPA treatment groups. At the effective concentration of BPA, histological analysis revealed pathological alterations of uterine morphology associated with a >5.3-fold increase in macrophage numbers in non-pyometra uteri of C57BL/6 mice exposed to BPA. These results suggest that BPA enhances immune responsiveness of the uterus and that heightened responsiveness in C57BL/6 females is related to increased susceptibility to pyometra.