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Maternal oxycodone treatment causes pathophysiological changes in the mouse placenta.

Madison T Green1, Rachel E Martin1, Jessica A Kinkade1

  • 1Christopher S Bond Life Sciences Center, University of Missouri, Columbia, MO, 65211, USA; Biomedical Sciences, University of Missouri, Columbia, MO, 65211, USA.

Placenta
|September 5, 2020
PubMed
Summary
This summary is machine-generated.

Maternal oxycodone (OXY) exposure alters placental structure and gene expression in a sex-specific manner. Female placentas upregulate protective genes, potentially shielding female offspring from long-term health issues.

Keywords:
AnalgesicDOHaDDrug abuseOpioidPlacental lactogensReproductionSexual dimorphismTrophoblastTrophoblast giant cells

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Area of Science:

  • Reproductive biology and developmental toxicology
  • Pharmacology and molecular biology
  • Obstetrics and gynecology

Background:

  • Opioid use during pregnancy, particularly oxycodone (OXY), poses risks to both mother and developing fetus.
  • The placenta, crucial for maternal-fetal communication, may be a key target for opioid-induced developmental effects.
  • Understanding placental responses to OXY is vital for assessing long-term offspring health outcomes.

Purpose of the Study:

  • To investigate the effects of maternal oxycodone (OXY) treatment on placental structure and gene expression patterns in a mouse model.
  • To determine if OXY-induced placental alterations are sex-dependent.
  • To explore the correlation between placental histological changes and gene expression profiles following OXY exposure.

Main Methods:

  • Female mice were administered daily doses of oxycodone (OXY) or saline (Control) for two weeks prior to breeding and throughout gestation.
  • Placentas were collected at embryonic day 12.5 for histological analysis and RNA sequencing (RNAseq).
  • Weighted correlation network analysis was used to correlate gene expression with histological findings.

Main Results:

  • Maternal OXY treatment reduced parietal trophoblast giant cell (pTGC) area and maternal blood vessel area in the placental labyrinth.
  • OXY exposure led to sex-specific placental gene expression changes: female placentas upregulated placental-enriched genes, while male placentas showed alterations in ribosomal proteins.
  • Gene expression changes in female placentas correlated with histological alterations, a correlation absent in male placentas.

Conclusions:

  • Maternal oxycodone exposure significantly alters placental histology and gene expression in a sex-dependent manner.
  • Female placentas exhibit a distinct response to OXY, upregulating specific transcripts that may offer protection to female offspring.
  • These findings highlight the placenta's role in mediating the developmental effects of maternal opioid exposure and suggest potential sex-based differences in offspring vulnerability.