Exposure to Zearalenone and its Impact on Maternal and Fetal Health

接触玉米赤霉烯酮及其对孕产妇和胎儿健康的影响

• 批准号: 10460821
• 负责人: Carolyn Kinkade
• 金额: $ 4.21万
• 依托单位: RUTGERS BIOMEDICAL AND HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10460821
• 关键词: 10 year old; 3-Hydroxysteroid Dehydrogenases; Age; Animal Model; Animals; Aromatase; Binding; Biological; Biological Assay; Biological Markers; Biological Models; Birth; CYP17A1 gene; Cattle; Chemical Structure; Child; Cohort Studies; Collection; Communication; Consumption; Data; Data Analyses; Data Collection; Diet; ESR1 gene; Endocrine; Endocrine Disruptors; Endocrine disruption; Endocrine system; Environmental Exposure; Enzymes; Epidemiology; Estradiol; Estriol; Estrogen Nuclear Receptor; Estrogen Receptor alpha; Estrogen Receptors; Estrogens; Estrone; European Union; Exposure to; Family suidae; Fellowship; Fetal Growth; Fetal health; First Pregnancy Trimester; Food; Food Contamination; Food Supply; Funding; Gonadal Steroid Hormones; Grain; Grant; Growth; Habitats; Hormones; Human; Human Development; Hydroxysteroid Dehydrogenases; Impairment; In Vitro; Infant; Infant Development; Infertility; Ingestion; International; Laboratories; Length; Linear Models; Liquid substance; Literature; Livestock; Maternal Health; Measures; Meat; Medical; Methods; Modeling; Mus; Mycotoxins; Nuclear Envelope; Outcome; Parents; Pathway interactions; Phenotype; Placenta; Plants; Population; Pregnancy; Pregnant Women; Prevalence; Progesterone Receptors; Property; Protein Analysis; Proteins; Public Policy; Rattus; Reproductive system; Research; Risk; Risk Assessment; Sampling; Science; Scientist; Signal Transduction; Skinfold Thickness; Source; Spontaneous abortion; Steroid biosynthesis; Testing; Tissues; Training; Translating; Urine; Vulnerable Populations; Weight Gain; Woman; Work; Writing; Zearalenone; Zeranol; adverse outcome; biological specimen archives; career; climate change; climate zone; cohort; cost effective; design; dietary; epidemiology study; estrogenic; exposed human population; fetal; gestational weight gain; girls; health of the mother; in vitro Model; in vivo; innovation; maternal serum; maternal weight; novel; offspring; perinatal outcomes; prenatal exposure; promoter; prospective; recruit; reproductive; sex; steroid hormone biosynthesis; urinary

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.

项目摘要/摘要 霉菌毒素粮食污染可能会因气候变化而加剧，这是一个日益增长的国际关注点。 真菌代谢产物Zearalenone（Zen）是一种内分泌干扰，通常在植物上发现的霉菌毒素 随着玉米和谷物在温度气候区域的生长。此外，尽管在欧盟被禁止 合成衍生物Zerool是在美国给牲畜施用的 美国暴露的来源。人类通过摄入受污染的谷物来源而暴露于ZEN和零 喂养污染饮食的动物的产品或产品。有大量的证据表明患病率 ZEN及其在食品和人类生物学液和暴露中的代谢产物预计将上升 随着气候变化的进一步变化，导致较温暖，潮湿的栖息地。涉及这种宽度曝光 它的化学结构与17β-雌二醇（E2）紧密相似，这使直接结合与核雌激素 受体α（ER-α）和β（ER-β）。 Zen及其代谢产物与雌激素受体结合的能力 他们的设计为“霉菌元”。在体内，大量证据表明，肌雌激素破坏了 大鼠，小鼠，牛和猪的内分泌和生殖系统，导致不良结果，例如 超雌激素，不育症，流产，妊娠体重增加降低和胎儿大小降低。体外证据 进一步表明禅宗破坏了性类固醇骑马的生物合成。考虑到广泛的影响 体内和体外模型系统中的内分泌效应以及无处不在的霉菌元暴露 全世界，人类迫切需要研究。该项目利用了一项前瞻性出生队列研究 （n = 326）在每个三个月都有生物循环收集，以检查暴露于mycoestogen的影响 产妇和胎儿健康结果。实验室测定在每种中量化母体尿液中的霉菌蛋白 妊娠中期以及术语placeta正在进行中。我们将使用这些数据来翻译体外和动物 神经植物暴露导致妊娠体重增加，循环循环的证据 水平和斑点性类固醇表达，人类出生时大小较小。我们将适合纵向回归 测试假设较高的神经雌激素浓度与循环降低有关的假设 怀孕期间的雌激素和妊娠体重增加。线性模型将告知 禅宗对类固醇生成标记物的胎盘表达，包括雌激素受体1（ESR1）的表达。 最后，我们将检查禅对婴儿大小的影响。这些研究对于风险评估很有价值 并将告知公共政策，以减少脆弱人群（婴儿，儿童）或期间的暴露 妊娠等敏感时期。