Transcriptomic Changes in Mouse Trophoblast Cells Following Oxycodone Exposure

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. Overall design: RNA samples were collected from either undifferentiated mouse trophoblast stem cells (mTSCs) or parietal trophoblast giant cells (pTGCs); the cells were treated with either 10 ug/mL oxycodone or 0.9% saline solution; each treatment group has four replicates; the mTSCs are a control against the pTGCs, and the saline treated samples are a control against the oxycodone-treated samples