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

• 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
• 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

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.

在过去的几十年里，全球环境温度稳步上升。气候温度升高会导致严重的极端事件，如热增加，导致哺乳动物物种的热应激、热休克和热衰竭。欧洲的研究显示了性别差异，在这种差异中，女性更容易死于热浪。同样，在动物中，雌性动物的生殖受到热应激导致的不孕不育的影响，表现为无排卵、受孕率下降和妊娠维持率低。与肥胖和多囊卵巢综合征(PCOS)等代谢紊乱类似，动物在HS期间会出现高胰岛素血症，我们的研究小组发现HS会改变卵巢胰岛素信号和类固醇激素的产生。在哺乳动物物种中，各种化合物改变内分泌信号，扰乱内源性激素的产生。这种内分泌干扰物是一种饮食污染物，玉米赤霉烯酮，它作为一种非类固醇雌激素，损害女性生殖。欧洲食品管理局已经确定了人类的接触情况；然而，美国没有确定这种情况。在不同的高胰岛素血症，肥胖的生理模型中，卵巢对环境中的卵毒暴露变得更加敏感。具体地说，罗奇女士将探索这样一种假设，即ZEA暴露会改变卵巢信号，热应激是ZEA诱导的卵毒性的附加因素。将使用猪的动物模型，因为猪和人类对ZEA暴露都有相似的敏感性，将完成两个具体目标。目标1将确定在HS期间暴露于ZEA的表型和内分泌影响。目的2将确定在HS期间暴露于ZEA是否改变卵巢的组织形态和参与卵泡发生、胰岛素信号转导、类固醇生成和细胞凋亡的途径。总的来说，这些实验将决定对单独和联合暴露ZEA和HS的表型和分子效应的全面理解。此外，该奖学金还将扩大Roach夫人的技术和智力能力，为她提供额外的科学和教学培训，以促进她在生殖生理学和毒物学专家的指导下的职业发展。这是一个利基和新兴的毒物学领域，罗奇女士将站在气候变化和毒物学交叉研究的前沿。总而言之，这项提案将支持克里斯特尔·罗奇女士在爱荷华州立大学动物科学系的研究和职业发展培训，该培训由艾琳·基廷博士赞助。