Abstract
OBJECTIVES: Opioid use during pregnancy is associated with adverse perinatal outcomes, but its effects on placental biology are not well understood. Because the placenta plays a vital role in fetal development and immune regulation, we examined how maternal opioid exposure influences microbial DNA signatures and immune gene expression in the placenta. METHODS: Placentas from opioid-exposed and control C57 BL/6 female mice were analyzed through 16S rRNA gene sequencing, bulk RNA sequencing and pathway enrichment analysis. RESULTS: Opioid-exposed placentas showed altered microbial DNA profiles, including increased α-diversity and enrichment of Staphylococcus spp. Transcriptomic analysis revealed 357 differentially expressed genes, emphasizing immune pathways, including dendritic cell-NK cell crosstalk, immunogenic cell death, and cytokine storm signaling. STAT3 signaling and heparan sulfate biosynthesis were downregulated. Pathways related to apoptosis, cytotoxicity, and neonatal death were upregulated. CONCLUSIONS: Maternal opioid exposure may disrupt placental microbial and immune environments, potentially leading to structural compromise through immune-mediated cellular apoptosis.