Model of xenoestrogen induction of mammary gland carcinogenesis. BPA binds to the
fetal mammary gland mesenchymal ERs and, in turn, affects the composition of the
extracellular matrix, which increases tissue rigidity and delays lumen
formation. BPA also induces precocious adipocyte differentiation, which in turn
accelerates duct elongation and branching. These changes lead to an increased
sensitivity to mammotropic hormones in adulthood. BPA also binds to ERs in the
hypothalamus, where it alters the control of ovarian cyclicity and secretion of
mammotropic hormones. Solid arrows link effects of in utero
exposure to BPA in rodents and nonhuman primates. Dashed arrows indicate
hypothesized links between effects during fetal mammary gland development and
mammary carcinogenesis. Abbreviations: BPA, bisphenol A; ERs, estrogen
receptors; HPOA, hypophyseal–pituitary–ovarian axis. Modified
with permission from Elsevier Ltd © Paulose, T. et al. Reprod.
Toxicol. 54, 58–65 (2014).