Talk abstracts
Talk on Tuesday 03:00-03:15pm submitted by Jillian Poska
In utero exposure to estrogenic bisphenol compounds affects the mammary gland microenvironment
Jillian M. Poska (Ohio State Biochemistry Program), Clarissa Wormsbaecher, Brittney M. Cumbia (Department of Molecular Genetics, James Comprehensive Cancer Center), Madeline R. Price (Department of Molecular Genetics), Marcos Cortes-Medina, Jacob Holter (James Comprehensive Cancer Center, Department of Biomedical Engineering), Jonathan W. Song (Department of Biomedical Engineering, Department of Mechanical and Aerospace Engineering)
Abstract:
In utero exposures to estrogenic endocrine disrupting compounds (EDCs) can increase breast cancer risk in adulthood. Bisphenol A (BPA) is an estrogenic EDC that alters mammary gland development and increases mammary gland tumorigenesis in rodent models following in utero exposure. Our lab has previously shown in utero BPA exposure induces alterations to the tissue microenvironment that are conducive to tumor initiation. Recent industrial standards have led to the replacement of BPA with various bisphenol analogues in commercial products that in many cases retain endocrine disruptor activity. However, it is unclear how these other bisphenol analogues act in utero and what molecular mechanisms drive changes to the microenvironment. In the present study, the mammary glands of mice exposed in utero to 1 of 8 bisphenol compounds or a vehicle control were evaluated for alterations in stromal and epithelial development. Changes to the microenvironment and their consequences were measured by collagen staining and tissue stiffness. We find that several BPA analogues cause increases in tissue stiffness following in utero exposure in a dose non-monotonic manner. We additionally investigated an epigenetic mechanism of developmental reprogramming as these alterations develop long after the exposure to these compounds. ATAC-seq in primary epithelial cells and fibroblasts revealed changes in chromatin accessibility in adult fibroblasts following in utero exposure to BPA. qRT-PCR of collagen genes at different timepoints follow in utero exposure was used to interrogate how alterations in gene expression in the microenvironment are propagated from womb to adulthood. Together, these studies provide insight into how EDCs influence mammary gland development and increase breast cancer risk following in utero exposure.
Keywords: endocrine disrupting compounds, breast cancer, fibroblasts