Single-cell RNA-sequencing analysis of estrogen- and endocrine-disrupting chemical-induced reorganization of mouse mammary gland.

ABSTRACT: Menopause is a critical window of susceptibility for its sensitivity to endocrine disrupting chemicals due to the decline of endogenous estrogen. Using a surgical menopausal (ovariectomized) mouse model, we assessed how mammary tissue was affected by both 17?-estradiol (E2) and polybrominated diphenyl ethers (PBDEs). As flame retardants in household products, PBDEs are widely detected in human serum. During physiologically-relevant exposure to E2, PBDEs enhanced E2-mediated regrowth of mammary glands with terminal end bud-like structures. Analysis of mammary gland RNA revealed that PBDEs both augmented E2-facilitated gene expression and modulated immune regulation. Through single-cell RNA sequencing (scRNAseq) analysis, E2 was found to induce Pgr expression in both Esr1 + and Esr1 - luminal epithelial cells and Ccl2 expression in Esr1 + fibroblasts. PBDEs promote the E2-AREG-EGFR-M2 macrophage pathway. Our findings support that E2?+?PBDE increases the risk of developing breast cancer through the expansion of estrogen-responsive luminal epithelial cells and immune modulation.

SUBMITTER: Kanaya N 

PROVIDER: S-EPMC6831695 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature