Maternal opioid use disorder: Placental transcriptome analysis for neonatal opioid withdrawal syndrome

Genomics. 2021 Nov;113(6):3610-3617. doi: 10.1016/j.ygeno.2021.08.001. Epub 2021 Aug 3.

Abstract

Excessive prenatal opioid exposure may lead to the development of Neonatal Opioid Withdrawal Syndrome (NOWS). RNA-seq was done on 64 formalin-fixed paraffin-embedded placental tissue samples from 32 mothers with opioid use disorder, with newborns with NOWS that required treatment, and 32 prenatally unexposed controls. We identified 93 differentially expressed genes in the placentas of infants with NOWS compared to unexposed controls. There were 4 up- and 89 downregulated genes. Among these, 7 genes CYP1A1, APOB, RPH3A, NRXN1, LINC01206, AL157396.1, UNC80 achieved an FDR p-value of <0.01. The remaining 87 genes were significant with FDR p-value <0.05. The 4 upregulated, CYP1A1, FP671120.3, RAD1, RN7SL856P, and the 10 most significantly downregulated genes were RNA5SP364, GRIN2A, UNC5D, DMBT1P1, MIR3976HG, LINC02199, LINC02822, PANTR1, AC012178.1, CTNNA2. Ingenuity Pathway Analysis identified the 7 most likely to play an important role in the etiology of NOWS. Our study expands insights into the genetic mechanisms of NOWS development.

Keywords: Differentially expressed genes; In utero drug exposure; Neonatal abstinence syndrome; Transcription factors; Transcriptional regulatory element.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics, Opioid / therapeutic use
  • Carrier Proteins
  • Female
  • Gene Expression Profiling
  • Humans
  • Infant
  • Infant, Newborn
  • Membrane Proteins
  • Neonatal Abstinence Syndrome* / complications
  • Neonatal Abstinence Syndrome* / drug therapy
  • Neonatal Abstinence Syndrome* / genetics
  • Opioid-Related Disorders* / drug therapy
  • Opioid-Related Disorders* / genetics
  • Placenta
  • Pregnancy

Substances

  • Analgesics, Opioid
  • Carrier Proteins
  • Membrane Proteins
  • Unc80 protein, human