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POPI: Placenta, Opioids and Perinatal Implications

POPI：胎盘、阿片类药物和围产期影响

基本信息

批准号：
10748428
负责人：
Ilhem Messaoudi
金额：
$ 301.12万
依托单位：
UNIVERSITY OF KENTUCKY
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-08-01 至 2026-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10748428
关键词：
Abstinence Address Admission activity Animal Model Appalachian Region Biochemical Markers Biological Markers Biometry Biophysics Birth Blood Blood specimen Brain Caring Cells Circulation Clinic Clinical Clinical Research Cognitive deficits Data Decidua Dedications Development Diagnosis Doppler Ultrasound Early Intervention Encephalitis Epigenetic Process Exposure to Fetal Development Fetal Growth Fetal Growth Retardation Fetal Reduction Fetus Gases Genetic Transcription Genomics Growth Head circumference Health Histologic Home Homeostasis Hospitalization Hour Human Image Immunology Impairment Incidence Infant Inflammation Inflammation Mediators Inflammatory Intervention Investigation Kentucky Knowledge Life Link Longitudinal Studies Low Birth Weight Infant Macrophage Maintenance Maternal-Fetal Exchange Maternal-fetal medicine Measurement Measures Mediating Microglia Modeling Molecular Mothers Motor Skills Neonatal Neonatal Abstinence Syndrome Neonatology Neurocognitive Neurocognitive Deficit Newborn Infant Nutrient Opioid Organoids Outcome PGF gene Pathology Pathway interactions Perinatal Phenotype Placenta Placentation Plasma Play Positioning Attribute Pregnancy Pregnant Women Premature Birth Production Publishing Reporting Research Research Design Risk Rodent Model Role Sampling Spontaneous abortion Substance Use Disorder Systems Biology Testing Tissues Umbilical Cord Blood United States Universities Variant Villous Withdrawal adverse outcome animal data brain health brain size brain tissue early childhood early pregnancy exosome experience experimental study fetal fetal opioid exposure indexing innovation insight maternal opioid use mental development monocyte multidisciplinary multimodality myelination neonate neurobehavioral neurodevelopment neuroinflammation neuroprotection neurotrophic factor novel offspring opioid epidemic opioid exposure opioid use disorder perinatal outcomes predictive modeling pregnant prenatal exposure programs transcriptomics trophoblast vascular factor

项目摘要

SUMMARY Maternal opioid use, which dramatically increased in recent years, exerts severe adverse consequences for the offspring’s health. Data from animal models and clinical studies demonstrated that prenatal opioid exposure is significantly associated with preterm birth, fetal growth restriction, low birth weights, neonatal opioid withdrawal syndrome, smaller brain sizes, and impaired neurobehavioral outcomes. However, the mechanistic underpinnings of these adverse outcomes remain poorly understood. Available published data and our preliminary studies strongly suggest that maternal opioid use disorder (OUD) perturbs the placenta-brain axis. One potential mechanism is that OUD disrupts placental development and function, impairing nutrient and gas exchange between mother and fetus. Another mechanism is that opioids accumulate in placental tissues, thereby directly disrupting normal fetal development. However, the molecular underpinnings and the contribution of each pathway remain poorly understood. Therefore, this application will test the central hypothesis that maternal OUD driven inflammation and dysregulation of the placental landscape are linked to adverse neurocognitive outcomes in the offspring. The novelty of this application lies in the systems biology approach that integrates phenotypic, functional, and genomic readouts at the maternal-fetal interface, umbilical cord blood at delivery, and neonatal blood with neurobehavioral and motor skill assessments throughout the first year of life. Completion of the proposed experiments will result in novel insights into the dysregulations of the placenta- brain axis elicited by maternal OUD and will pave the way to building a comprehensive construct and inform the development of early interventions during opioid-exposed pregnancies.

总结近年来，母体阿片类药物的使用急剧增加，后代的健康。来自动物模型和临床研究的数据表明，产前阿片类药物暴露是与早产、胎儿生长受限、低出生体重、新生儿阿片类药物戒断显著相关综合征，较小的大脑尺寸和受损的神经行为结果。然而，机械对这些不良后果的基础仍然知之甚少。现有的公布数据和我们的初步研究强烈表明，母体阿片类药物使用障碍（OUD）扰乱胎盘-大脑轴线一个潜在的机制是OUD破坏胎盘发育和功能，损害营养和母亲和胎儿之间的气体交换。另一个机制是阿片类药物在胎盘组织中积累，从而直接破坏正常的胎儿发育。然而，分子基础和贡献对每一种途径的了解仍然很少。因此，本申请将检验中心假设，母体OUD驱动的炎症和胎盘景观的失调与不利的神经认知的结果。这种应用的新奇在于系统生物学方法在母胎界面整合表型、功能和基因组读数的脐带血在分娩时，新生儿血液与神经行为和运动技能评估在整个第一年的生活完成拟议的实验将导致对胎盘失调的新见解- 脑轴引起的母亲OUD，并将铺平道路，建立一个全面的结构，并告知在暴露于阿片类药物的妊娠期间制定早期干预措施。