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：拟议的研究是关于气候变化对健康的影响，特别是与女性相关的健康影响。瘦和肥胖女性的生殖和总体健康。由于肥胖影响了约 40% 的女性，并且该提案对少数族裔女孩和妇女产生了不成比例的影响，该提案与健康公平方面相关气候变化和健康倡议。这项工作涉及\已确定的相关领域的理解气候变化引起的压力对生殖和发育的影响，并评估多种化学物质（DMBA）和非化学压力（肥胖和热应激）贯穿整个生命周期。气候变化和严重 HS 事件的伴随频率有增无减，因此，了解 HS 对卵巢的影响功能是迫切需要的。基廷博士在这项研究中拥有独特的地位，因为她在卵巢生物学的这一领域（二十篇关于热应激生物学的出版物，其中大多数与复制）以及进行这些研究的技术可行性。假设热应激会导致高胰岛素血症、改变卵巢类固醇生成、DNA 修复、氧化应激和化学物质生物转化蛋白丰度，在 DMBA 暴露期间加速卵巢毒性，这将相对于瘦小鼠，肥胖小鼠的该值升高。这个假设是基于我们强有力的初步数据雌性猪生物医学模型以及与肥胖期间观察到的代谢变化的相关性。这补充品将产生数据，为未来探索热应激对身体的附加影响铺平道路。使用易于处理的小鼠模型深入研究特定途径来研究卵毒性。