5 years ago

Varying susceptibility of the female mammary gland to in utero windows of BPA exposure.

Claire E Kovalchin, Hannah L Helber, Abigail M Fagan, Nanditha Ravichandran, Craig J Burd, Pamela M St. John, Alina R Murphy, Xiaokui Molly Mo, Andrea R Hindman
In utero exposure to the endocrine disrupting compound bisphenol A (BPA) is known to disrupt mammary gland development and increase tumor susceptibility in rodents. It is unclear if there are different periods of in utero development that may be more susceptible to BPA exposure. Herein, pregnant CD-1 mice were exposed to BPA at different times during gestation that correspond to specific milestones of in utero mammary gland development. Mammary glands of early-life and adult female mice, exposed in utero to BPA, were morphologically and molecularly (ERα and Ki67) evaluated for developmental abnormalities. We found that BPA treatments occurring prior to mammary bud invasion into the mesenchyme (embryonic day (E), E12.5) incompletely resulted in the measured phenotypes of mammary gland defects.Exposing mice up to the point in which the epithelium extends into the precursor fat pad (E16.5) resulted in a nearly complete BPA phenotype while exposures during epithelial extension (E15.5-18.5) resulted in a partial phenotype. Furthermore, the relative differences in phenotypes between exposures highlights significant correlations between early-life molecular changes (ERα and Ki67) in the stroma and the epithelial elongation defects in mammary development. These data further implicate BPA action in the stroma as a critical mediator of epithelial phenotypes.

Publisher URL: http://doi.org/10.1210/en.2017-00116

DOI: 10.1210/en.2017-00116

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