Investigating additive impact of heat stress on zearalenone-induced ovotoxicity

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，如热量增加，导致哺乳动物热应激（HS）、热休克和热衰竭。欧洲的研究显示了性别差异，女性更容易死于热浪。同样，在动物中，雌性生殖受到热应激引起的不育的损害，表现为无排卵、受孕率降低和妊娠维持时间低。与肥胖和多囊卵巢综合征（PCOS）等代谢性疾病类似，HS期间的动物是高胰岛素血症，我们的研究小组发现HS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，破坏内源性激素的产生。这种内分泌干扰物是一种膳食污染物，玉米赤霉烯酮，它作为一种非甾体雌激素，损害女性生殖。欧洲食品管理局已确定人类接触；然而，这在美国是不成立的。在高胰岛素血症、肥胖等不同的生理模型中，卵巢对环境卵毒性暴露更加敏感。具体来说，罗奇女士将探讨ZEA暴露会改变卵巢信号的假设，以及热应激对ZEA诱导的卵巢毒性的附加作用。由于猪和人类对ZEA暴露具有相似的敏感性，因此将使用猪动物模型，并将完成两个具体目标。目的1将确定HS期间ZEA暴露的表型和内分泌影响。目的2将确定在HS期间暴露于ZEA是否会改变卵巢组织形态学和涉及卵泡发生、胰岛素信号、类固醇发生和细胞凋亡的途径。总的来说，这些实验将确定对ZEA和HS单独或联合暴露的表型和分子效应的全面理解。此外，该奖学金将扩大罗奇女士的技术和智力能力，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理学专家的指导下的职业发展。这是一个利基和新兴的毒理学领域，这将使罗奇女士站在气候变化和毒理学交叉的最前沿。综上所述，本提案将支持爱荷华州立大学动物科学系Crystal Roach女士在Aileen Keating博士的赞助下进行研究和职业发展培训。

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.