Effects of exposure to ethinyl estradiol during pregnancy and lactation on the postinvolution mammary gland

The mammary gland undergoes extensive reorganization during pregnancy, lactation, and involution. During involution, mass apoptosis of epithelial cells and infiltration of immune cells return the gland to a state similar to the nulliparous female. However, the postinvolution gland has structural differences to the nulliparous gland, which may provide protection against breast cancer. Changes associated with parity are hormone dependent and could be vulnerable to endocrine-disrupting chemicals, particularly those that are estrogen receptor (ER) agonists.

We evaluated the effects of ethinyl estradiol (EE2), a pharmaceutical ER agonist, administered during pregnancy and lactation on the structure and steroid function of the postinvolution mammary gland.

CD-1 mice were exposed to vehicle or EE2 (20 μg/kg/day) from pregnancy day 9 until weaning. An unexposed nulliparous group was included for comparison. Five weeks after exposure, we evaluated the mammary glands for treatment effects on tissue architecture, proliferation, immune cell populations, and steroid function.

EE2 exposure reduced the parity-driven effects on mammary gland epithelial volume, with more modest (nonsignificant) effects on mammary gland functional components including a reduction in resident macrophages, an increase in ER- and a decrease in progesterone receptor-expressing cells. EE2 exposure also restricted maternal and pup growth during the exposure period and delayed pup eye opening.

These results suggest that EE2 exposure during pregnancy and lactation disrupts some of the typical changes of parity seen in the mammary gland. This pharmaceutical may provide insights into effects of other estrogenic endocrine-disrupting chemicals on the maternal mammary gland.