Placental origins of phthalate-induced changes in fetal reproductive development

邻苯二甲酸盐引起的胎儿生殖发育变化的胎盘起源

基本信息

批准号：
10392572
负责人：
Jennifer Joan Adibi
金额：
$ 53.89万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-13 至 2022-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10392572
关键词：
Administrative Supplement Advisory Committees Anxiety Biological Biological Markers Birth Brain COVID-19 COVID-19 pandemic Chorionic Gonadotropin Chronic Cities Collection Communities Complement Consumption Data Data Analyses Diabetes Mellitus Diet Discrimination Endocrine Endocrine Disruptors Environment Environmental Exposure Etiology Exposure to Food Gestational Age Gestational Diabetes Glucose Goals Gonadotropins Grant Growth Health Healthcare Healthcare Systems Heart Diseases Human Chorionic Gonadotropin Hypertension Hypothalamic structure Immune Infant Mortality Inflammatory Intervention Lead Light Maternal Exposure Maternal Health Maternal Mortality Measures Mediator of activation protein Mental Depression Messenger RNA Metabolism Methods Modeling Molecular Mothers Neurosecretory Systems Outcome Outcome Measure Pathway interactions Personal Satisfaction Physiological Pituitary Gland Pituitary Gonadotropins Pituitary-Adrenal System Placenta Population Population Heterogeneity Postpartum Period Pre-Eclampsia Predisposition Pregnancy Pregnancy Complications Pregnancy Outcome Pregnant Women Premature Birth Premature Labor Process Public Health Questionnaires Race Reproduction Research Research Personnel Risk SARS-CoV-2 exposure SARS-CoV-2 infection Sampling Serotonin Serum Source Stress Structural Racism Sum Testing Thyrotropin Tissues Translating Translational Research United States National Institutes of Health Weather Weight Weight Gain Woman Work base black women blood glucose regulation cohort design experience fetal follow-up food environment food insecurity human tissue hypothalamic-pituitary-adrenal axis insight maternal morbidity maternal serum maternal stress molecular marker novel pandemic disease phthalates postnatal postpartum health pregnancy health pregnant prenatal prenatal exposure reproductive development stressor therapy design waist circumference

项目摘要

1 During pregnancy, the maternal brain and the fetal-placental unit are connected by way of an understudied 2 hypothalamic-pituitary-placental (HPP) axis. This axis may shed light on the differential effects of stress 3 exposure on maternal and fetal well-being complementing what we already know about the hypothalamic- 4 pituitary-adrenal (HPA) axis. The COVID-19 pandemic has aggravated the chronic maternal stressors arising 5 from structural racism and discrimination in the U.S., and has also heightened disparities in food insecurity and 6 SARS-CoV-2 infection. Stress and adversity in pregnancy not only increase risks of preterm birth, growth 7 restriction and infant mortality, but they also heighten risk of postpartum maternal mortality and morbidity too 8 (i.e., diabetes, heart disease, depression). To gain insight into the etiology of these dramatic changes in 9 exposure and susceptibility at the population level, we propose to ‘join the army’ organized by the NIH 10 Maternal Mortality Task Force, of interdisciplinary investigators generating and analyzing data in racially and 11 economically diverse populations, at different stages of reproduction, and in different tissue types. We will 12 extend our R01 (ES029336-03) research in the following ways: 1) to broaden the definition of maternal 13 environmental exposure to the endocrine disrupting chemicals phthalates to include food insecurity and 14 changing food environments (correlated with consumption of ultra-processed and packaged foods which 15 contain phthalates), maternal stress, structural racism and discrimination, and SARS-CoV-2 exposure and 16 related immune and inflammatory effects at the maternal-placental interface; 2) to examine a novel endocrine 17 axis that connects the maternal hypothalamus and pituitary with the fetal placenta by studying gonadotropins in 18 maternal serum (prenatal/postnatal) and in placental tissue; and 3) to estimate and compare the direct and 19 indirect pathways (through placental-pituitary gonadotropins) from maternal prenatal exposures to maternal 20 postpartum health. Postpartum health will be measured as pregnancy complications (preeclampsia and 21 hypertension, gestational diabetes and glucose regulation, placental accrete and abruptio, preterm labor and 22 gestational age at delivery) and by follow-up measures in the first year postpartum (glucose levels, 23 anthropometrics related to weight gain and metabolism, measures of depression, anxiety, stress, 24 discrimination and food insecurity). We will use existing R01 data from two cohorts (UPSIDE MPIs Barrett, 25 O’Connor and Magee CT PI Simhan) to establish a conceptual model, and apply this model to the context of 26 the COVID-19 pandemic and SRD in Pittsburgh with collection of new data from 100 pregnancies of Black and 27 White women, who conceived since March 2020 and delivered since June 2020. In sum, this work will 28 generate insight into sources of adversity in pregnancy, unique to being Black and/or pregnant during the 29 COVID-19 pandemic; and to offer a public health strategy applicable to a city at the 97th percentile of 30 postpartum maternal mortality among Black women in the U.S

1在怀孕期间，孕产妇大脑和胎儿 - 替代单位通过理解连接 2下丘脑 - 垂体 - 置换（HPP）轴。该轴可能会阐明压力的差异影响 3关于孕产妇和胎儿健康的暴露，完成了我们已经知道的下丘脑的知识 4个垂体 - 肾上腺（HPA）轴。 COVID-19大流行汇总了慢性物质应激源 5来自美国的结构性种族主义和歧视，还增加了粮食不安全和 6 SARS-COV-2感染。怀孕的压力和广告不仅增加了早产的风险 7限制和婴儿死亡率，但也提高了产后材料死亡率和发病率的风险 8（即糖尿病，心脏病，抑郁症）。洞悉这些戏剧性变化的病因 9在人口一级的暴露和敏感性，我们建议“加入NIH的军队” 10跨学科研究人员生成和分析种族和分析数据的孕产妇死亡率工作组在经济多样的种群中，在不同的繁殖阶段和不同的组织类型中。我们将 12扩展了我们的R01（ES029336-03）研究以下方式：1）扩大母体的定义 13环境暴露于内分泌的邻苯二甲酸化学物质，包括粮食不安全和 14不断变化的食物环境（与消费超级加工和包装食品有关 15包含邻苯二甲酸盐），材料压力，结构性种族主义和歧视以及SARS-COV-2暴露以及 16孕产妇界面的相关免疫和炎症作用； 2）检查新型内分泌 17轴通过研究促性腺激素在 18层血清（产后/产后）和放置组织； 3）估计和比较直接和从母体产前暴露于母体 20产后健康。产后健康将被衡量为妊娠并发症（先兆子痫和 21高血压，妊娠糖尿病和葡萄糖调节，斑点腹和破裂，早产和 22分娩时胎龄）和产后第一年的随访措施（葡萄糖水平， 23与体重增加和新陈代谢有关的人类计量学，抑郁，焦虑，压力的度量 24歧视和粮食不安全）。我们将使用来自两个队列的现有R01数据（Upside MPIS Barrett， 25 O'Connor和Magee Ct Pi Simhan）建立一个概念模型，并将此模型应用于 26匹兹堡的COVID-19-19大流行和SRD，收集了100个黑人怀孕的新数据 27名白人妇女，自2020年3月以来一直构思并自2020年6月以来交付。总而言之，这项工作将 28对怀孕的广告来源产生洞察力，在黑人和/或怀孕期间独有 29 Covid-19-19;并提供适用于城市的公共卫生战略 30美国黑人妇女的产后死亡率