In utero exposure to estrogenic bisphenol analogues increases mammary tissue stiffness

In utero exposures to estrogenic endocrine disrupting compounds (EDCs) can increase breast cancer risk in adulthood. It has previously been shown that the estrogenic plasticizer bisphenol A (BPA) alters development of the mammary gland and increases both mammary gland stiffness and tumor susceptibility in rodent models following in utero exposure. Because of its endocrine disrupting properties, BPA has been substituted with structural analogues with varying abilities to activate estrogen receptor alpha (ERα). However, the impact of in utero exposure to many of these analogues is unknown. In the present study, we aimed to analyze the impact of bisphenol analogues on collagen deposition and mammary gland stiffness and characterize mammary epithelial development following exposure to these compounds. With the exception of bisphenol S, all analogues significantly increased mammary gland stiffness at a 25 µg/kg body weight dose in a manner that correlated to estrogenic activity. In contrast, significant effects on epithelial development endpoints were limited and did not follow a clear pattern. These results add to the growing literature on the hazard of bisphenol analogues and support the idea that these compounds promote abnormal mammary gland development. Furthermore, these data support a model that bisphenol compounds induce a microenvironment that may promote breast cancer development in an estrogen-dependent manner.