POPI: Placenta, Opioids and Perinatal Implications

摘要 近年来，母体阿片类药物的使用急剧增加，对 为了后代的健康。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，脑体积变小，神经行为结果受损。然而，机械论 这些不利后果的基础仍然鲜为人知。可用的已发布数据和我们的 初步研究强烈表明，母体阿片类药物使用障碍(OUD)扰乱了胎盘-大脑 轴心。一种可能的机制是OUD扰乱胎盘的发育和功能，损害营养和 母亲和胎儿之间的气体交换。另一种机制是阿片类药物在胎盘组织中积聚， 从而直接扰乱了胎儿的正常发育。然而，分子基础和贡献 对每条途径的研究仍然知之甚少。因此，这个应用程序将测试以下中心假设 母体OUD引发的炎症和胎盘景观的失调与不良 后代的神经认知结果。这一应用的新奇之处在于系统生物学方法。 它整合了母胎界面的表型、功能和基因组读数，即脐带血 在分娩时，并在第一年进行神经行为和运动技能评估的新生儿血液 生活。拟议中的实验的完成将带来对胎盘失调的新见解-- 脑轴由母体引出，将为构建一个全面的结构和信息 阿片类药物暴露孕期早期干预措施的发展。

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.