Multimodal analysis of gestational health and placental injury in opioid-affected pregnancies

Active Project Grant Awarded Last action

Award ID
R01DA059176
Recipient
Awarding agency
Obligated
$4,634,294

Award facts

Assistance listing
93.279 Drug Use and Addiction Research Programs
Completion date 65% complete
Originally
Place of performance
Washington, DC 20010, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
Opioids are medically used for safe pain relief and management. However, illicit opioid use has substantially increased across the US in the past decade, with further worsening during the covid-19 pandemic, leading to a profound impact on human health. Specifically, opioid use disorder (OUD) during pregnancy poses an increased risk of pregnancy-associated maternal morbidity and mortality, fetal growth restriction (FGR) and related complications, neonatal opioid withdrawal syndrome, and long-term neurobehavioral effects. Some of these risks persist despite the use of safer opioids, such as buprenorphine and methadone, medications for OUD (MOUD) patients. Whereas current studies center mainly on transplacental opioid transport to the fetus and the adverse effects of opioids on infants, the direct impact of illicit and prescription opioids on placental development, differentiation, and function are largely unexplored. The placental floating villi mediate maternal- fetal gas exchange, nutrient uptake, waste release immune defense and the production of hormones and extracellular vesicles (EVS). These villi are covered by a layer of multinucleated, terminally differentiated syncytiotrophoblasts (STBS), which forms the feto-placental frontline that is directly exposed to opioids in the maternal blood. Subjacent to this layer are mononucleated, progenitor cytotrophoblasts (CTBS), which replenish the STB layer through the process of differentiation and fusion. Importantly, injuries to the STB and CTB layers are implicated in pregnancy-associated complications, including FGR and stillbirth. Here we seek to investigate opioid-dependent placental injury, focusing on the most critical and unique layer of placental trophoblasts. We will enroll participants with OUD, including illicit opioids and MOUD (buprenorphine, methadone), examine their pregnancy course and their children's health through the first year postpartum. Using biospecimens from each participant, including maternal plasma and urine across the three trimesters, placental biopsies and fetal cord blood at delivery, we will employ multimodal cutting-edge technologies, including single-cell rnaseq, spatial transcriptomics, protein chip cytometry and placenta EV RNA profiling, and explore the molecular and cellular processes affected by opioids in the maternal-placental-fetal trio- ecosystem. To gain mechanistic insights into the functional changes in gene expression and EV cargo, we will use an array of model systems, including human trophoblast stem cells and cultured primary human trophoblasts, and mechanistically interrogate pathways underlying opioid injury. We will further correlate key molecular signatures with clinical assessment, including maternal gestational disorders, perinatal and infant neurodevelopmental outcomes. Together, our strategic plan, bolstered by our transdisciplinary team, enables US to address critically important knowledge gaps related to human placenta biology in opioid-affected pregnancies.

Transactions

Action Obligated Date
Amendment $964,853
Amendment $0
Amendment $0
Amendment $1,247,483
Amendment $1,247,483
Amendment -$958,842
Amendment -$958,842
Original award $3,092,159

Subawards

Subrecipient Amount Awarded
Magee-Womens Research Institute And Foundation Multimodal Analysis of Gestational Health and Placental Injury in Opioid-Affected Pregnancies $375,225
Magee-Womens Research Institute And Foundation $322,100
University Of Pittsburgh - Of The Commonwealth System Of Higher Education $133,128
The Leland Stanford Junior University $54,584
University Of Pittsburgh - Of The Commonwealth System Of Higher Education Multimodal Analysis of Gestational Health and Placental Injury in Opioid-Affected Pregnancies - PROJECT SUMMARY Opioids are medically used for safe pain… $546,073

Quick answers

Who received award R01DA059176?

R01DA059176 was awarded to Children's Research Institute by National Institute on Drug Abuse (National Institutes of Health) on August 15, 2023.

How much is award R01DA059176 worth?

$4,634,294 has been obligated on R01DA059176.

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