Investigating obesity-induced altered ovarian intracellular signaling

摘要：提出的研究是关于气候变化对健康的影响，特别是与女性有关

Abstract: The research proposed is on Health Effects of climate change, specifically related to female reproductive and general health, in lean and obese females. Since obesity affects ~40% of women, and disproportionately impacts minority girls and women, this proposal is relevant to the Health Equity aspects of the climate change and health initiative. This work addresses \ the identified relevant areas of understanding the effects of climate-change-induced stress on reproduction and development and assesses multiple chemical (DMBA) and non-chemical stressors (obesity and heat stress) across the lifespan. Climate change and accompanying frequency of severe HS events is unabating, thus, understanding impacts of HS on ovarian function is desperately needed. Dr. Keating is uniquely positioned for this study due to her scientific record in this area of ovarian biology (twenty publications on heat stress biology with the majority related to reproduction) and the technical feasibility to conduct these studies. The hypothesis is that heat stress will cause hyperinsulinemia, altering ovarian steroidogenic, DNA repair, oxidative stress and chemical biotransformation protein abundance, accelerating ovarian toxicity during DMBA exposure, and this will be heightened in obese relative to lean mice. This hypothesis is based upon our strong preliminary data in female pig biomedical models and the relevance to the metabolic changes observed during obesity. This supplement will generate data to pave the way for future exploration into the additive impact of heat stress on ovotoxicity using tractable mouse models to delve into specific pathways.