SAT640 Maternal Preconception Exposure Leads To The Propagation Of Disease

Disclosure: D.D. Davis: None. R. Chamorro-Garcia: None. C. Diaz-Castillo: None. Tobacco products harbor a heterogeneous cluster of endocrine-disrupting chemicals (EDCs) that can lead to many adverse health effects, including obesity and other metabolic diseases. During critical developmental windows, exposure to EDCs found in tobacco products, including inorganic arsenic (iAs) and nicotine, can increase susceptibility to these diseases. An understudied window of significant influence on the susceptibility to developing adverse health effects in future generations is during maternal preconception (i.e., maternal preconception exposure, MPE). MPE involves essential processes of maternal germline development, such as oogenesis and folliculogenesis. Oogenesis begins at birth with an oogonium and goes through a maturation process that either ends after ovulation as a secondary oocyte or, if fertilized, becomes a zygote. Concurrently, folliculogenesis occurs and is the process by which the oocyte develops within the ovarian follicle into a mature egg. This ovarian follicle consists of many somatic cells that contribute to the maturation of the oocyte via paracrine mechanisms. We found that female offspring of mothers exposed to 200 µg/mL nicotine and male offspring exposed to both nicotine and a combination of 10 µg/L iAs + 200 µg/mL nicotine during MPE had higher weights during early development. Females whose mothers were exposed to 10 µg/L iAs showed an insulin resistance phenotype after intraperitoneal injection of insulin. Interestingly in males from mothers that were exposed to 10 µg/L iAs and 200 µg/mL nicotine we found impaired glucose tolerance after intraperitoneal injection of glucose. These data support the hypothesis that MPE is a critical window of susceptibility to metabolically associated diseases later in life. Future directions involve expanding the previously stated experiment by performing in vitro fertilization and embryonic implantation in mothers not exposed to our chemical treatment. The goal of this will be to investigate if the offsprings have similar health outcomes to the mice born of natural fertilization, which, if they do, would indicate the alterations were occurring before fertilization. We also aim to determine the mechanisms that trigger the phenotypes observed in the F1. We will analyze alterations of the somatic cells of the antral follicle and oocyte before ovulation by performing transcriptomic analyses. Presentation: Saturday, June 17, 2023