Investigating additive impact of heat stress on zearalenone-induced ovotoxicity

研究热应激对玉米赤霉烯酮诱导的卵毒性的附加影响

基本信息

批准号：
10315882
负责人：
Crystal Michelle Roach
金额：
$ 3.96万
依托单位：
IOWA STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-08-01 至 2023-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10315882
关键词：
1-Phosphatidylinositol 3-Kinase Adolescent Adult Animal Model Animals Anovulation Apoptosis Apoptotic Area Barley Biological Body Temperature Body Weight Cardiovascular system Cessation of life Chemicals Climate Competence Conceptions Crystallization Data Development Endocrine Endocrine Disruptors Endocrine disruption Endotoxemia Environmental Health Enzyme-Linked Immunosorbent Assay Estradiol Estrogens Estrus Europe European Event Experimental Models Exposure to Family suidae Fellowship Female Female infertility Fertility Food Food Contamination Fusarium Goals Health Heat Exhaustion Heat Stress Disorders Heat Waves Heat-Shock Response Hormonal Human Hyperinsulinism Impairment Infertility Insulin Intake Intestines Investigation Iowa Italy Link Malnutrition Measures Mentors Mentorship Messenger RNA Metabolic Diseases Metabolism Molecular Morbidity - disease rate Mycotoxins NOEL Non-Steroidal Estrogens Nuts Obesity Oral Ovarian Ovary Pathway interactions Phenotype Physiological Planets Polycystic Ovary Syndrome Population Positioning Attribute Precocious Puberty Pregnancy Maintenance Production Prolactin Proteins Proteomics Quantitative Reverse Transcriptase PCR Reproduction Reproductive Physiology Research Research Support Respiration Science Serum Signal Transduction Steroid biosynthesis Structure Temperature Time Toddler Toxicant exposure Toxicology Training United States Universities Vector-transmitted infectious disease Weather Western Blotting Wheat Woman Zearalenone absorption adverse outcome authority base career development climate change climate impact contaminated water dietary estrogenic experience experimental study exposed human population extreme weather female fertility folliculogenesis gender difference girls improved insulin signaling mortality novel ovotoxicant ovotoxicity physiologic model prepuberty reproductive function research and development respiratory steroid hormone stressor

项目摘要

Global ambient temperatures have steadily increased over the past decades. Increased climate temperatures cause severe extreme incidents, such as increased thermal heat, causing heat-stress (HS), heat shock, and heat exhaustion among mammalian species. European studies show gender differences, in which women are more susceptible to death by heatwaves. Likewise, in animals, female reproduction is compromised by heat- stress induced infertility, phenotypically noted as anovulation, reduced conception rate, and low pregnancy maintenance. Resembling metabolic disorders such as obesity and polycystic ovarian syndrome (PCOS), animals during HS are hyperinsulinemic, and our research group have discovered that HS alters ovarian insulin signaling and steroid hormone production. In mammalian species, various compounds alter endocrine signaling disrupting endogenous hormonal production. Such an endocrine disruptor is a dietary contaminant, zearalenone, which acts as a non-steroidal estrogen to impair female reproduction. Human exposure has been identified in the European Food Authority; however, such is not established in the United States. In a different physiological model of hyperinsulinemia, obesity, the ovary becomes more sensitive to environmental ovotoxic exposures. Specifically, Ms. Roach will explore the hypothesis that ZEA exposure alters ovarian signaling and that heat stress is additive to ZEA-induced ovotoxicity. A pig animal model will be used since both pigs and humans have similar sensitivities to ZEA exposure, and two specific aims will be completed. Aim 1 will determine the phenotypic and endocrine impacts of ZEA exposure during HS. Aim 2 will determine if exposure to ZEA during HS alters ovarian histomorphology and pathways involved in folliculogenesis, insulin signaling, steroidogenesis, and apoptosis. Collectively, these experiments will determine a comprehensive understanding of phenotypic and molecular effects of ZEA and HS exposures alone and in combination. In addition, this fellowship will expand Mrs. Roach's technical and intellectual competencies by providing her with additional scientific and didactic training to enhance her career development under the mentorship of an expert in reproductive physiology and toxicology. This is a niche and emerging area of toxicology that will position Ms. Roach to be at the forefront of the intersection between climate change and toxicology. In all, this proposal will support the research and career development training of Ms. Crystal Roach in the Department of Animal Science at Iowa State University under the sponsorship of Dr. Aileen Keating.

在过去的几十年中，全球环境温度稳步升高。气候温度的升高会导致严重的极端事件，例如增加热量，导致热压力（HS），热休克和哺乳动物物种的热量耗尽。欧洲研究表明，性别差异，其中女性更容易受到热浪的死亡。同样，在动物中，女性繁殖受到热应力引起的不育症的损害，表型被视为发肠，构造率降低和妊娠降低。类似于肥胖和多囊卵巢综合征（PCOS）等代谢性疾病，HS期间的动物是高胰岛素的，我们的研究小组发现HS会改变卵巢胰岛素信号传导和类固醇激素的产生。在哺乳动物物种中，各种化合物改变内源性激素产生的内分泌信号传导。这种内分泌破坏者是一种膳食污染物Zearalenone，它是一种非甾体类雌激素来损害女性繁殖。在欧洲食品管理局中已经确定了人类的暴露；但是，在美国没有建立这种情况。在高胰岛素血症的不同生理模型中，卵巢对环境卵毒性暴露更加敏感。具体而言，罗奇女士将探讨玉米菌暴露会改变卵巢信号的假设，并且热应激是ZEA诱导的产卵毒性的添加剂。猪动物模型将被使用，因为猪和人类都具有与ZEA暴露相似的敏感性，并且将完成两个特定的目标。 AIM 1将确定HS期间ZEA暴露的表型和内分泌影响。 AIM 2将确定在HS期间暴露于ZEA是否会改变卵巢组织形态和参与卵泡发生，胰岛素信号传导，类固醇生成和凋亡的途径。总的来说，这些实验将确定单独和组合ZEA和HS暴露的表型和分子效应的全面理解。此外，该奖学金将通过为她提供其他科学和教学培训来扩大罗奇夫人的技术和知识能力，从而在生殖生理学和毒理学专家的指导下增强她的职业发展。这是毒理学的一个利基和新兴领域，将罗奇女士定位为气候变化与毒理学之间交叉的最前沿。总的来说，该提案将支持爱荷华州立大学动物科学系Crystal Roach女士在Aileen Keating博士的赞助下的研究和职业发展培训。