Investigating additive impact of heat stress on zearalenone-induced ovotoxicity

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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.