SAT-460 Do Endocrine-Disrupting Chemicals Cause Heritable Changes in Reproduction?

Abstract D.L. Sheinhaus: None. Successful reproduction depends upon a precise homeostasis involving hormones and their actions on the reproductive tract. These processes can be perturbed by environmental toxicants such as endocrine-disrupting chemicals (EDCs), which are associated with reproductive diseases. EDCs are ubiquitous environmental toxicants present in food and beverages, pesticides, medical tubing, and personal care products, among other sources. Early life development (fetus and infant) are amongst the most susceptible populations to EDCs, as disrupting hormones during these hormonally sensitive periods can significantly affect the developmental origins of health and disease. This project focuses on how EDC exposures during development cause epigenetic molecular programming of the reproductive tract in males, setting the stage for reproductive abnormalities. Work is conducted on the epididymis, where sperm travel from caput to cauda and undergo final stages of maturation. Part of the maturation process includes interaction with their surrounding environment, including extracellular vesicles (EVs). EVs of the epididymis, named epididymosomes, bud off of cellular membranes and are released into epididymal fluid. Epididymosomes transmit signals that play an important role in sperm development via molecular cargo that can be transmitted to sperm, causing changes to the latter’s gene expression and function, and affect reproductive outcomes. Our experiment uses a rat model to investigate how EDCs reprogram epididymal EV molecular contents. Rats are bred and pregnant dams are fed with a mixture of common EDCs. This exposes not only the dam but also her fetuses (F1 generation) and within the fetuses, the cells that will eventually become sperm or ova and (F2 generation). Male offspring are monitored for development and in adulthood, they are euthanized to collect and isolate epididymal EVs and sperm for subsequent RNA sequencing. I hypothesize that exposure to EDCs during development impairs male reproductive capacity through epigenetic programming, subsequently perturbing sperm maturation. Future work will determine how EDCs influence RNA and DNA of sperm in the epididymis. Saturday, June 1, 2024