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Investigating obesity-induced altered ovarian intracellular signaling

研究肥胖引起的卵巢细胞内信号传导改变

基本信息

批准号：
10837744
负责人：
Aileen Frances Keating
金额：
$ 10.04万
依托单位：
IOWA STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-01-01 至 2024-10-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10837744
关键词：
AHR gene ATM activation Acceleration Address Affect Anthracenes Antioxidants Area Aromatic Polycyclic Hydrocarbons Biology ChIP-seq Chemical Exposure Chemicals Conceptions Congenital Abnormality DNA Adduction DNA Adducts DNA Damage DNA Repair DNA Repair Gene Data Development Diet Enzymes Estrus Event Exposure to Family suidae Fatty acid glycerol esters Female Fertility Foundations Frequencies Functional disorder Future Generations Goals Health Heat Stress Disorders Hyperinsulinism Hyperphagia Infertility Investigation Learning Longevity Maintenance Malignant neoplasm of ovary Metabolic Metabolic Biotransformation Methylation Minority Minority Groups Minority Women Modeling Mus Neonatal Obese Mice Obesity Outcome Ovarian Ovarian Follicle Ovary Oxidative Stress Oxidative Stress Induction PIK3CG gene Pathway interactions Periodicity Phenotype Positioning Attribute Proteins Publications Reactive Oxygen Species Reproduction Reproductive Health Research Risk Role Signal Transduction Societies Solid Specific qualifier value Spontaneous abortion Stress Subfecundity Thinness Woman Women&apos s Health Work ataxia telangiectasia mutated protein climate change climate-related health dimethylbenzanthracene feeding female fertility girls health equity histone modification implantation improved in utero interest mouse model novel offspring oocyte quality ovarian damage ovotoxicant ovotoxicity prepuberty promoter reproductive reproductive success response risk minimization socioeconomics stressor sugar tool transcriptome sequencing

项目摘要

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.

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