# Maternal opioid use is associated with altered placental bacterial DNA and activation of immune-apoptotic pathways

## TL;DR

Maternal opioid use during pregnancy changes the placenta's microbial and immune profiles, which could harm fetal development.

## Contribution

This study reveals how maternal opioid exposure alters placental microbial DNA and activates immune-apoptotic pathways in mice.

## Key findings

- Opioid-exposed placentas showed increased microbial diversity and more Staphylococcus spp.
- Immune-related pathways like dendritic cell-NK cell crosstalk and cytokine storm signaling were upregulated.
- Apoptosis and cytotoxicity pathways were elevated, while STAT3 and heparan sulfate biosynthesis were reduced.

## Abstract

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.

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.

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.

Maternal opioid exposure may disrupt placental microbial and immune environments, potentially leading to structural compromise through immune-mediated cellular apoptosis.