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

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 >4000 μg/kg-d or 17α-ethinyl estradiol (EE; 1.2 to >150 μg/kg-d). In the C57BL/6 strain, pyometra occurred in the 15 μg/kg-d EE and 33 μg/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.

► Sensitivity for aversion to diet containing EE was identified.
► C57BL/6 mice are susceptible to estrogen-induced pyometra.
► CD1 mice do not develop pyometra when exposed to estrogens or bisphenol A.
► Bisphenol A presumably acts as an estrogen to cause pyometra at a “low dose”.
► Bisphenol A exposure correlates with an increase in uterine macrophage infiltration.