Emerging Mycoestrogens: Impacts on Placental and Early Childhood Growth

新兴的真菌雌激素：对胎盘和儿童早期生长的影响

• 批准号: 10400907
• 负责人: Zorimar Rivera-Nunez
• 金额: $ 19.56万
• 依托单位: RBHS-SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-04 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10400907
• 关键词: Abdomen; Address; Affect; Affinity; Age; Age-Months; Agonist; Animal Model; Animals; Apoptosis; Area; Basic Science; Binding; Biometry; Birth; Birth Weight; Blood Vessels; Caliber; Cell Proliferation; Characteristics; Chemicals; Child; Child Development; Child Health; Data; Detection; Development; Endocrine Disruptors; Endocrine Glands; Endocrine disruption; Environmental Exposure; Estrogen Receptor alpha; Estrogen Receptors; European Union; Exposure to; Female Adolescents; Femur; Fetal Growth; Fetal Weight; Fetus; First Pregnancy Trimester; Food Supply; Grain; Growth; Growth Factor; Head circumference; Health; Health Policy; Hormones; Human; Impairment; Infant; Infant Health; Infrastructure; Intake; Lead; Length; Light; Livestock; Measurement; Measures; Mediating; Mediator of activation protein; Morphology; Mycotoxins; Non-Steroidal Estrogens; Outcome; Pathway interactions; Perinatal; Placenta; Placentation; Pregnancy; Pregnant Women; Production; Property; Public Health; Research; Rodent; Role; Sampling; Second Pregnancy Trimester; Skinfold Thickness; Source; Stress; Support System; Surface; Testing; Thick; Third Pregnancy Trimester; Time; Tissues; Toxic effect; Toxin; Translating; Urine; Weight; Woman; Work; World Health Organization; Zearalenone; Zeranol; analytical method; base; cohort; cost; critical period; dietary; early childhood; environmental chemical; epidemiology study; estrogenic; experience; exposed human population; fetal; fetus nutrition; fungus; girls; global temperature; immunohistochemical markers; in utero; infant outcome; innovation; mouse model; novel; offspring; placental morphology; pregnancy health; prenatal; prenatal exposure; promoter; protein metabolism; reproductive; trophoblast; ultrasound

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.

项目摘要 世界卫生组织称Zearalenone（ZEN），通常在食品供应中发现，一个 最关心的霉菌毒素。 Zeranol（Zer），一种用于促进牲畜生长的Zen的合成形式， 由于既定的内分泌中断特性，因此在欧盟被禁止。 Zen和 ZER与雌激素受体α和β结合具有更高亲和力的α与其他良好研究的内分泌干扰 化学物质（EDC），以“肌脱脂蛋白”的形式获得了设计。在子宫内暴露于禅宗和Zer 破坏后代的发展，导致胎儿减轻和出生体重。霉菌剂对婴儿的影响 健康可能会提早开始，随着plapeta的发展改变。作为激素和增长的主要来源 胎儿不断增长的因素，plapeta是环境化学物质破坏的敏感靶标。我们的 来自小鼠模型的实验数据表明，位置重量和表面积的减少以及 Zen暴露后突触化途径的改变。尽管动物模型中的这项令人信服的作品 迄今为止，尚无流行病学研究的人类对这些化合物的暴露宽度的证据 检查了霉菌元对儿童健康的影响。提议的总体假设 研究是，子宫内的神经源性暴露会不利地影响斑点的发育并损害 胎儿和婴儿的生长。作为正在进行的上升研究的一部分，我们将测试我们的中心假设 怀孕队列研究了plapeta在产前之间的介导关系中的作用 儿童的暴露和早期发育（n = 326）。我们将在尿液和斑点中量化霉菌元 跨多个时间点的组织（第一，第二和第三个三物以及出生）。然后我们将检查材料 与Upside的综合放置数据有关的mycoestogen浓度，其中包括：（1）基本 胎盘尺寸特征（例如重量，表面积，厚度，体积和直径）； （2）新颖的胎盘 终点（例如血管表面积和血管分支点的数量）和（3）免疫组织化学 滋养细胞应力的标记（例如凋亡和细胞增殖）。 围产期生长我们将基于第二个和第三学期将新型的mycoestrogen数据与胎儿生物特征分析进行比较 超声检查以及婴儿在出生时纵向收集的1、6,12、24和36个月大。 这将是首次全面评估母子，胎儿和婴儿预后的流行病学研究 在暴露神经膜的情况下，将为公共卫生政策提供与越来越多的存在和 全球粮食供应中霉菌毒素的管理。