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Perinatal opioid exposure and outcomes of exposed offspring in early adolescence

ABSTRACT: The opioid epidemic has received considerable attention, but the impact on perinatal opioid-exposed (POE) offspring remains underexplored. This study addresses the emerging public health challenge of understanding and treating POE children. We examine two scenarios using preclinical models: offspring exposed to oxycodone (OXY) in utero (IUO) and postnatally (PNO). We hypothesized exposure to OXY during pregnancy primes offspring for neurodevelopmental deficits and severity of deficits is dependent on timing of exposure. Notable findings include reduced head size and brain weight in offspring. Molecular analyses revealed significantly lower levels of inflammasome-specific genes in the prefrontal cortex (PFC). Gene Set Enrichment Analysis (GSEA) and Ingenuity Pathway Analysis (IPA) highlighted the enrichment of genes associated with mitochondrial and synapse dysfunction in POE offspring. Western blot analysis validated IPA predictions of mitochondrial dysfunction in PFC-derived synaptosomes. Behavioral studies identified significant social deficits in POE offspring. This study presents the first comparative analysis of PNO- and IUO-offspring during early adolescence finding PNO-offspring have considerably greater deficits. The striking difference in deficit severity in PNO-offspring suggests that exposure to opioids in late pregnancy pose the greatest risk for offspring well-being.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE265842 | GEO | 2024/04/25

REPOSITORIES: GEO

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