Mycoestrogens and maternal-child health in the TIDES cohort

The accumulation of mycotoxins, chemical by-products of fungal growth, is an emerging issue in public health due to their widespread presence in food systems. Mycotoxins contaminate crops worldwide and their prevalence will increase as ecosystems become warmer and wetter. One of the most common mycotoxins, zearalenone (ZEN), derives from Fusarium species and is widely detected in cereal grains, grain-based products, meat, milk, wine, beer, dried fruit, and spices. ZEN and its metabolites bind to estrogen receptors earning their designation as ‘mycoestrogens’. In livestock and experimental models, ZEN exposure dysregulates maternal and offspring hormone signaling, alters gestational weight gain, and disrupts offspring growth and pubertal trajectories. Despite the large and compelling toxicological literature and the near ubiquitous human exposure, alarmingly little is known about ZEN’s impacts on human health. In the first epidemiological study of its kind, we recently observed that higher urinary ZEN concentrations in U.S. pregnant women were associated with sexdependent differences in circulating estrogens in pregnancy, greater gestational weight gain, and altered infant size. These findings have led us to the overarching hypothesis that developmental mycoestrogen exposure disrupts steroidogenic and metabolic activity in humans, leading to sex-specific alterations in child growth. What is now urgently needed are studies that more extensively characterize both prenatal and childhood exposures to ZEN in large, diverse samples with further exploration of mechanistic pathways and extended follow-up into adolescence. Here, we fill those gaps and advance the limited epidemiological research on ZEN by leveraging existing data and biospecimens from TIDES (The Infant Development and the Environment Study), a deeply-phenotyped, multi-site U.S. cohort that recruited pregnant women from 2010-2012. Using existing data and biospecimens from the full TIDES cohort (494 mother-child dyads), we will examine prenatal and childhood exposures to ZEN and its metabolites in relation to (a) steroidogenesis and metabolomics in pregnancy; and (b) child growth from birth through adolescence. This will be the first study to examine the potential health impacts of prenatal and childhood exposure to mycoestrogens in U.S. mothers and children. Leveraging the uniquely suited TIDES cohort, we address national mandates to examine variation by sex and provide sorely needed information on emerging mycoestrogen exposures. We anticipate that results may help identify harms and inform mitigation strategies to reduce exposures as well as efforts to regulate mycoestrogens in the food supply in the U.S. and beyond.