Abstract
Menopause is considered a critical window of susceptibility (WOS) for its sensitivity to endocrine-disrupting chemicals due to decline of endogenous estrogen. Using a surgical menopausal (ovariectomized) mouse model, we assessed how mammary gland tissue was affected by both 17β-estradiol (E2) and polybrominated diphenyl ethers (PBDEs). These endocrine-disrupting chemicals have been used as flame retardants in common household products since the 1970s and are vastly detected in human serum. During physiologically relevant exposure to E2, PBDEs enhanced E2-mediated regrowth of mammary glands with terminal end budlike structures. To better elucidate the effects of E2 and PBDEs, single-cell RNA sequencing (scRNAseq) analysis was performed. In a definitive manner, E2 was found to induce Pgr expression in both Esr1+ and Esr1- cells. We identified PBDE-impacted cell populations, Esr1+/Pgr+ and Esr1-/Pgr+ cells, in both mature luminal epithelial and progenitor cells, as well as the mammary gland population of M2 macrophages. Significantly, scRNAseq data show gene expression differences among cells with differential expression of Esr1 and Pgr. The results help clarify how exposure to both E2 and endocrine-disrupting chemicals like PBDEs after menopause impacts mammary gland structure. Ultimately, the findings advance understanding of how such exposure can increase the risk of developing breast cancer through the expansion of estrogen-responsive cells. (Supported by NIH U01ES026137.)
Citation Format: Shiuan Chen, Noriko Kanaya, Gregory Chang, Xiwei Wu, Kohei Saeki, Lauren Bernal, Timothy Dynold, Susan L. Neuhausen. Single-cell RNA-sequencing analysis of estrogen and the endocrine-disrupting chemical induced mouse mammary gland reorganization after surgical menopause [abstract]. In: Proceedings of the AACR Special Conference on Environmental Carcinogenesis: Potential Pathway to Cancer Prevention; 2019 Jun 22-24; Charlotte, NC. Philadelphia (PA): AACR; Can Prev Res 2020;13(7 Suppl): Abstract nr A30.
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