Emerging Mycoestrogens: Impacts on Placental and Early Childhood Growth

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PROJECT SUMMARY The World Health Organization has called zearalenone (ZEN), commonly found in the food supply, one the mycotoxins of greatest concern. Zeranol (ZER), a synthetic form of ZEN used to promote growth in livestock, has been banned in the European Union because of established endocrine-disrupting properties. Both ZEN and ZER bind to estrogen receptors α and β with higher affinity than other well-studied endocrine-disrupting chemicals (EDCs), earning their designation as ‘mycoestrogens’. In utero exposure of animals to ZEN and ZER disrupts offspring development, causing reduced fetal and birth weight. The impact of mycoestrogens on infant health may start early, with altered development of the placenta. As the principal source of hormones and growth factors for the growing fetus, the placenta is a sensitive target for disruption by environmental chemicals. Our experimental data from a mouse model indicates reduction in placental weights and surface area along with alteration of syncytialization pathways following ZEN exposure. Despite this compelling work in animal models and evidence of widespread human exposure to these compounds, to date, no epidemiological research has examined the impact of mycoestrogens on children’s health. The overarching hypothesis of the proposed research is that mycoestrogen exposure in utero adversely affects placental development and impairs fetal and infant growth. We will test our central hypothesis as part of the ongoing UPSIDE study, a U.S.-based pregnancy cohort that investigates the role of the placenta in mediating relationships between prenatal exposures and early development of children (n=326). We will quantify mycoestrogens in urine and placental tissue across multiple time points (1st, 2nd and 3rd trimesters and birth). We will then examine maternal mycoestrogen concentrations in relation to UPSIDE’s comprehensive placenta data, which includes: (1) basic placental size characteristics (e.g. weight, surface area, thickness, volume, and diameter); (2) novel placental endpoints (e.g. vascular surface area and number of vascular branch points) and (3) immunohistochemical markers of trophoblast stress (e.g., apoptosis and cell proliferation).To study the impact of mycoestrogens on perinatal growth we will compare novel mycoestrogen data to fetal biometry based on 2nd and 3rd trimester ultrasounds as well as infant anthropometric collected longitudinally at birth, 1, 6,12, 24 and 36 months of age. This will be the first epidemiological study to comprehensively assess maternal, fetal, and infant outcomes following mycoestrogen exposure and will inform public health policy related to the increasing presence and management of mycotoxins in the global food supply.