Endocrine disrupting chemicals and the mammary gland

Development of the mammary gland requires coordination of hormone signaling pathways including those mediated by estrogen, progesterone, androgen and prolactin receptors. These hormones play important roles at several distinct stages of life including embryonic/fetal development, puberty, pregnancy, lactation, and old age. This also makes the gland sensitive to perturbations from environmental agents including endocrine disrupting chemicals (EDCs). Although there is evidence from human populations of associations between EDCs and disruptions to breast development and lactation, these studies are often complicated by the timing of exposure assessments and the latency to develop breast diseases (e.g., years to decades). Rodents have been instrumental in providing insights-not only to the basic biology and endocrinology of the mammary gland, but to the effects of EDCs on this tissue at different stages of development. Studies, mostly but not exclusively, of estrogenic EDCs have shown that the mammary gland is a sensitive tissue, that exposures during perinatal development can produce abnormal mammary structures (e.g., alveolar buds, typically seen in pregnant females) in adulthood; that exposures during pregnancy can alter milk production; and that EDC exposures can enhance the response of the mammary tissue to hormones and chemical carcinogens. Other studies of persistent organic pollutants have shown that EDC exposures during critical windows of development can delay development of the gland, with lifelong consequences for the individual. Collectively, this work continues to support the conclusion that EDCs can harm the mammary gland, with effects that depend on the period of exposure and the period of evaluation.