Exposure to Zearalenone and its Impact on Maternal and Fetal Health

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Project Summary/Abstract Mycotoxin food contamination, potentially exacerbated by climate change, is a growing international concern. The fungal metabolite, zearalenone (ZEN), is an endocrine-disrupting mycotoxin commonly found on plants such as corn and grains grown in the temperate climate zone. Additionally, although banned in the European Union, the synthetic derivative, zeranol, is administered to livestock in the U.S. making meat consumption an additional source of U.S. exposure. Humans are exposed to ZEN and zeranol by ingesting contaminated grain-derived products or products from animals fed contaminated diets. There is a large body of evidence on the prevalence of ZEN and its metabolites in food products and in human biological fluids and exposure is expected to rise further with climate change leading to warmer, wetter habitats. This widespread exposure is concerning given that its chemical structure closely resembles 17β-estradiol (E2) which enables direct binding to nuclear estrogen receptors α (ER-α) and β (ER-β). The ability of ZEN and its metabolites to bind to estrogen receptors earned their designation as `mycoestrogens'. In vivo, substantial evidence demonstrates that mycoestrogens disrupt the endocrine and reproductive systems in rats, mice, cows, and pigs, leading to adverse outcomes such as hyperestrogenism, infertility, miscarriage, lower gestational weight gain, and reduced fetal size. In vitro evidence further demonstrates that ZEN disrupts sex steroid hormone biosynthesis. Given the wide-ranging impact of endocrine-disrupting effects in vivo and in vitro model systems and ubiquitous exposure to mycoestrogens worldwide, humans studies are urgently needed. This project capitalizes on a prospective birth cohort study (n=326) with biospecimen collection at each trimester, to examine the impact of mycoestrogen exposure on maternal and fetal health outcomes. Laboratory assays to quantify mycoestrogens in maternal urine in each trimester as well as term placenta are ongoing. We will use those data to translate the in vitro and animal evidence that mycoestrogen exposure leads to reduced gestational weight gain, altered circulating hormone levels and placental sex steroid expression, and smaller size at birth in humans. We will fit longitudinal regression models to test the hypothesis that higher mycoestrogen concentrations are associated with decreased circulating estrogens during pregnancy and reduced gestational weight gain. Linear models will inform on the impact of ZEN on placental expression of steroidogenic markers including expression of estrogen receptor 1 (ESR1). Finally, we will examine impacts of ZEN on infant size at birth. These studies will be valuable for risk assessment and will inform public policy to reduce exposure among vulnerable populations (infants, children) or during sensitive periods such as gestation.