PILOT: EFFECT OF MATERNAL EXPOSURES ON FETAL GROWTH, METABOLISM, AND DEVELOPMENT

试点：母亲暴露对胎儿生长、代谢和发育的影响

基本信息

批准号：
8638801
负责人：
Samantha F Butts
金额：
$ 12.76万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/8638801
关键词：
Adult Affect Animals Assisted Reproductive Technology Attention Barker Hypothesis Biological Markers Birth Clinical Trials Conceptions DNA Data Development Developmental Gene Diabetes Mellitus Diagnostic Diet Dimensions Disease Education Embryo Endocrine Disruptors Environment Environmental Exposure Epidemiology Epigenetic Process Female Fertility Fetal Growth Fetal Growth Retardation Fetus Folate Folic Acid Gene Expression Genes Growth Growth and Development function Health Homeostasis Hormones Human Hypertension IGFBP3 gene Infertility Insulin Investigation Lead Leptin Life Link Literature Low Birth Weight Infant Maternal Deprivation Maternal Exposure Measures Metabolic Metabolic Diseases Metabolism Micronutrients Modification Neonatal Nutritional Organ Outcome Ovarian Ovary Pathway interactions Pattern Physiology Pilot Projects Placenta Predisposition Pregnancy Production Recruitment Activity Reproduction Reproductive Health Reproductive Medicine Risk Sampling Testing Therapeutic Clinical Trial Time Tissues Turner&apos s Syndrome Umbilical Cord Blood Vascular Diseases Vitamin B 12 Vitamin D Weight Woman Work base bisphenol A clinical practice cohort conditioning design developmental plasticity disorder risk egg embryo/fetus epidemiologic data fetal hormone metabolism hormone sensitivity imprint in utero mullerian-inhibiting hormone neonate non-genomic obesity risk postnatal premature programs prospective reproductive reproductive success response theories

项目摘要

The developmental origins of adult disease hypothesis has gained strength as a powerful explanation for risk of some of the most prevalent and morbid human conditions. According to this theory, risk of disease in adulthood is initially induced by fetal responses to maternal conditions and exposures. Central to the developmental origins hypothesis is the concept of developmental plasticity which involves altered gene expression as a result of non-genomic modifications to DNA. Growing evidence supports the concept that developmental programming may occur from a window that spans periconception through postnatal life. Epidemiologic data supporting a relationship between assisted reproductive technologies, low birth-weight and rare conditions involving imprinted genes makes it plausible that additional exposures around the time of conception may also impact fetal growth. The full impact of impaired fetal growth may not be completely evident until years after birth when later developmental and reproductive milestones can be affected. We hypothesize that specific maternal exposures around the time of conception and in utero are associated with neonatal markers of metabolism, development and ovarian function. This study will measure several maternal exposures around conception and in utero that may impact developmental plasticity and post natal disease risk. Maternal levels of folate, vitamin B12, Vitamin D and the endocrine disrupting chemical Bisphenol-A will be measured. Cohorts of fertile women, infertile women seeking treatment will be recruited for study. At birth, neonatal weight and placental dimensions will be measured. Samples of cord blood from neonates will also be collected to measure biomarkers of metabolism (leptin, 1GF1, IFG2, Insulin, IGFBP3) and ovarian function (Anti-Mullerian Hormone). Results from this pilot study should help us design an appropriately powered clinical trial with the potential for the Reproductive Medicien Network to undertake.

成人疾病的发育起源假说已成为对风险的有力解释一些最普遍和最病态的人类状况。根据这一理论，患病风险成年期最初是由胎儿对母体条件和暴露的反应引起的。中心到发育起源假说是发育可塑性的概念，涉及基因改变 DNA 非基因组修饰的结果。越来越多的证据支持这一概念：发育规划可能发生在从围孕期到产后生活的一个窗口。流行病学数据支持辅助生殖技术与低出生体重之间的关系涉及印记基因的罕见情况使得在受孕也可能影响胎儿的生长。胎儿生长受损的全部影响可能并不完全直到出生后数年才会明显，此时以后的发育和生殖里程碑可能会受到影响。我们假设怀孕期间和子宫内的特定母亲接触与具有代谢、发育和卵巢功能的新生儿标志物。这项研究将测量几个受孕前后和子宫内的母亲接触可能影响发育可塑性和产后疾病风险。叶酸、维生素 B12、维生素 D 和内分泌干扰化学物质的母体水平将测量双酚-A。将招募寻求治疗的生育妇女和不孕妇女群体用于学习。出生时，将测量新生儿体重和胎盘尺寸。脐带血样本来自还将收集新生儿来测量代谢生物标志物（瘦素、1GF1、IFG2、胰岛素、IGFBP3）和卵巢功能（抗缪勒氏管激素）。这项试点研究的结果应该有助于我们设计一项具有适当动力的临床试验，并有可能生殖医学网承办。