Altered Mammary Gland Development and Pro-Tumorigenic Changes in Young Female Mice Following Prenatal BPAF Exposure

Bisphenol A (BPA) is being phased out owing to its endocrine-disrupting effects and is increasingly being replaced by its substitute compounds such as bisphenol AF (BPAF). This study aims to explore the potential adverse outcomes of prenatal BPAF exposure combined with postnatal cross-fostering on the development and long-term health effects of the mammary gland in offspring. The results suggested that prenatal BPAF exposure accelerates the puberty, and induces duct dilatations, angiogenesis, lobular hyperplasia, and enhanced inflammatory cell infiltration in the mammary gland of female offspring. Differentially expressed genes exhibiting time series patterns induced by BPAF exposure were enriched in biological processes related to mammary gland development, epithelial cell proliferation and so on. Notably, 13 breast cancer-related biomarkers including Pgr, Gata3, Egfr and Areg were screened, showing a time-dependent increase in expression. After human homologous gene transformation, TCGA analysis suggested that the human homologues of genes differentially expressed in BPAF-treated mice were associated with increased tumor stages in female patients with breast cancer. Furthermore, postnatal cross-fostering did not completely restore the adverse effects of prenatal BPAF exposure and even showed a reverse tendency. These results imply that prenatal BPAF exposure in utero and postnatally nursing by BPAF exposed dams, have long-term effects on the mammary glands health of female offspring.