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.

项目概要 世界卫生组织将食品供应中常见的玉米赤霉烯酮 (ZEN) 称为“玉米赤霉烯酮”之一。 最受关注的霉菌毒素。玉米赤霉醇 (ZER) 是 ZEN 的合成形式，用于促进牲畜生长， 由于已确定的内分泌干扰特性，已在欧盟被禁止。禅宗和 ZER 与雌激素受体 α 和 β 的结合亲和力高于其他经过充分研究的内分泌干扰物 化学物质（EDC），被称为“真菌雌激素”。动物在子宫内暴露于 ZEN 和 ZER 扰乱后代发育，导致胎儿和出生体重减轻。真菌雌激素对婴儿的影响 随着胎盘发育的改变，健康可能会提早开始。作为激素和生长的主要来源 作为胎儿生长的重要因素，胎盘是环境化学物质破坏的敏感目标。我们的 小鼠模型的实验数据表明胎盘重量和表面积的减少以及 ZEN 暴露后合胞化途径的改变。尽管动物模型方面的工作引人注目 以及人类广泛接触这些化合物的证据，迄今为止，还没有流行病学研究发现 研究了真菌雌激素对儿童健康的影响。所提出的总体假设 研究表明，子宫内接触霉菌雌激素会对胎盘发育产生不利影响并损害 胎儿和婴儿的生长。我们将测试我们的中心假设，作为正在进行的 UPSIDE 研究的一部分，该研究是一项总部位于美国的研究 妊娠队列研究胎盘在调节产前关系中的作用 儿童的暴露和早期发育（n=326）。我们将量化尿液和胎盘中的霉菌雌激素 跨多个时间点（第一、第二和第三个三个月以及出生）的组织。然后我们会检查产妇 与 UPSIDE 综合胎盘数据相关的霉菌雌激素浓度，其中包括：(1) 基本 胎盘大小特征（例如重量、表面积、厚度、体积和直径）； (2)新型胎盘 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 滋养层应激的标志物（例如细胞凋亡和细胞增殖）。研究真菌雌激素对 围产期生长，我们将根据妊娠第二和第三个月将新的真菌雌激素数据与胎儿生物测定数据进行比较 在出生时、1、6、12、24 和 36 个月时纵向收集超声检查以及婴儿人体测量数据。 这将是第一项全面评估孕产妇、胎儿和婴儿结局的流行病学研究 暴露于真菌雌激素后，并将为与日益增加的存在和相关的公共卫生政策提供信息 全球食品供应中霉菌毒素的管理。