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Transcriptomic Changes in Mouse Trophoblast Cells Following Oxycodone Exposure

ABSTRACT: Pregnant women are increasingly being prescribed and others are abusing opioid drugs. Neonates prenatally exposed to opioids are at risk for neonatal abstinence syndrome (NAS) that is linked with poor fetal and infant outcomes and possible diseases later in life. As the primary communication organ between mother and conceptus, the placenta is potentially vulnerable to opioid effects but may be key to understanding how these drugs affect long-term offspring health and how poor health outcomes may be ameliorated in utero. We have demonstrated maternal oxycodone (OXY) treatment in mice reduced parietal trophoblast giant cell (pTGC) area. OXY exposure affected placental gene expression profiles, including genes unique to the placenta. These gene expression patterns correlated with placental histological changes induced by OXY. We hypothesize that particular trophoblast (TB) cells of the mouse, most likely the pTGC, and probably certain TB subpopulations of the human placenta are particularly vulnerable to OXY exposure. To follow-up on these results, effects of OXY on transcriptome profiles of TB stem cells (TSC) and those differentiated into pTGC were examined and compared to control counterparts. Findings reveal OXY exposure induced distinct transcriptomic change in TSC and pTGC. Transcripts altered in TSC are generally enriched in the embryonic brain, whereas, those affected in the pTGC, including several prolactin and cathepsin forms, are associated with the placenta. Data suggest developmental exposure to OXY might alter similar gene-sets in TSC and the developing brain. Such findings may thus provide early diagnostic biomarkers and targets to prevent diseases associated with opioid-exposed NAS.

ORGANISM(S): Mus musculus

PROVIDER: GSE220248 | GEO | 2025/12/01

REPOSITORIES: GEO

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Project description:Purpose: The goals of this study are to examine how maternal exposure to oxycodone affects the global transcriptome and histological structure of the mouse placenta at 12.5 dpc of pregnancy.retinal transcriptome profiling (RNA-seq) to microarray and quantitative reverse transcription polymerase chain reaction (qRT–PCR) methods and to evaluate protocols for optimal high-throughput data analysis Methods: A high throughput RNA sequencing method was used to examine the global transcriptomic changes affected by oxycodone in male and female conceptuses. Histomorphometrics were used to assess the various regions of the placenta, namely the labyrinth, spongiotrophoblast, and parietal trophoblast giant cell (pTGC) region. The open-sourced software, weighted correlation network analysis (WGCNA) was used to link gene expression changes and histological (phenotypic) changes. Results: Using an optimized data analysis workflow, we mapped over 40 million sequence reads per sample to the mouse genome (build grcm38). An average of 95.6% of reads (38.7 million) was mapped with HISAT2 workflow. We identified 12,138 transcripts in the placenta of saline control and oxycodone mice with featureCounts workflow. One hundred eighty-eight transcripts showed differential expression between the OXY male vs. CTL male placenta, with a log2Foldchange ≥1 and p value <0.05. Fifty-eight transcripts showed differential expression between the OXY female vs. CTL female placenta, with a log2Foldchange ≥1 and p value <0.05. Hierarchical clustering of differentially expressed genes uncovered several genes that may contribute to placenta function. Conclusions: Our study represents the first detailed analysis of placental transcriptomes in oxycodone-exposed mice, with biologic replicates, generated by RNA-seq technology. The data analysis workflows reported here should provide a framework for comparative investigations of expression profiles. We conclude that oxycodone exposure changed transcriptome characterization and these changes were associated with placenta histological features.

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Transcriptomic Changes in Mouse Trophoblast Cells Following Oxycodone Exposure

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