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A Pilot Multiplex Salivary Transcriptomic Analysis to Understand the Sex-specific Effects of Maternal Opioid Use in
Tomoko Kaneko-Tarui1, Francesca Carasi-Schwartz1, Kiran Singh1
1Tufts Medical Center.
Insights
Maternal opioid use impacts neonates differently based on sex. Opioid exposure upregulated reward and inflammation pathways in males, while downregulating them in females, affecting health outcomes.
Area of Science:
- Neonatal development
- Molecular biology
- Perinatal health
Background:
- Opioid use disorder (OUD) exhibits sex-specific effects, but neonatal molecular mechanisms remain understudied.
- Previous research indicates differential opioid effects on neonatal reward and inflammatory pathways, potentially impacting growth and cardiometabolic health.
Purpose of the Study:
- To investigate the sex-specific molecular impacts of maternal opioid use during pregnancy on offspring.
- To examine effects on reward, energy homeostasis, inflammation, oxidative stress, and neuropathology pathways.
Main Methods:
- Observational pilot study involving nine opioid-exposed and nine non-exposed neonates.
- Multiplex, high-throughput analysis of 72 select genes in neonatal saliva using NanoString's nCounter® system.
- Optimization of experimental conditions for low RNA abundance in neonatal saliva.
Main Results:
- Demonstrated sex-specific molecular effects of maternal opioid use.
- Upregulated pathways (reward, inflammation, oxidative stress, feeding, energy homeostasis) observed in males.
- Downregulated pathways (inflammation, cardiovascular function) observed in females.
Conclusions:
- Maternal opioid use has sex-specific molecular consequences in neonates.
- Neonatal saliva multiplexing via high-throughput platforms is feasible.
- Further research with larger samples is needed to validate findings and clarify long-term health impacts.
Abstract:
Opioid use disorder affects males and females differently, yet the molecular mechanisms are understudied in neonates. Our laboratory has demonstrated differential sex effects of opioids on the reward and inflammatory pathways related to neonatal feeding behavior that may affect growth and cardiometabolic outcomes. This observational pilot study examined the sex-specific impact of maternal opioid use during pregnancy on reward, energy homeostasis, inflammation, oxidative stress, and neuropathology pathways in offspring. Saliva from nine opioid-exposed and nine non-exposed neonates collected within 48 hours after birth underwent a multiplex, high-throughput analysis of 72 select genes using NanoString's nCounter® system (NanoString Technologies, Seattle, WA, USA. Despite low RNA abundance in neonatal saliva, experimental conditions were optimized after several trials. Multiplex analysis demonstrated sex-specific molecular effects of maternal opioid use, i.e., upregulated pathways related to reward, inflammation, oxidative stress, feeding, and energy homeostasis pathways in males, and downregulated pathways related to inflammation and cardiovascular function in females. This pilot study demonstrates the feasibility of multiplexing neonatal saliva using a high-throughput platform. Future work will replicate these methods and validate findings in a larger sample to clarify the sex-specific short and long-term impact of maternal opioid use on health outcomes.
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