Placental dysfunction is associated with altered microRNA expression in pregnant women with low folate status

Research output: Contribution to journalArticle

Authors

  • Bernadette Baker
  • Samantha Lean
  • Susan Greenwood
  • Alexander Heazell
  • Karen Forbes
  • Rebecca Jones
  • Fiona MacKie

Colleges, School and Institutes

External organisations

  • University of Manchester
  • Division of Reproduction and Early Development, Leeds Institute of Cardiovascular and Metabolic Medicine

Abstract

Scope Low maternal folate status during pregnancy increases the risk of delivering small for gestational age (SGA) infants, but the mechanistic link between maternal folate status, SGA, and placental dysfunction is unknown. microRNAs (miRNAs) are altered in pregnancy pathologies and by folate in other systems. We hypothesized that low maternal folate status causes placental dysfunction, mediated by altered miRNA expression. Methods and results A prospective observational study recruited pregnant adolescents and assessed third trimester folate status and placental function. miRNA array, QPCR, and bioinformatics identified placental miRNAs and target genes. Low maternal folate status is associated with higher incidence of SGA infants (28% versus 13%, p < 0.05) and placental dysfunction, including elevated trophoblast proliferation and apoptosis (p < 0.001), reduced amino acid transport (p < 0.01), and altered placental hormones (pregnancy-associated plasma protein A, progesterone, and human placental lactogen). miR-222-3p, miR-141-3p, and miR-34b-5p were upregulated by low folate status (p < 0.05). Bioinformatics predicted a gene network regulating cell turnover. Quantitative PCR demonstrated that key genes in this network (zinc finger E-box binding homeobox 2, v-myc myelocytomatosis viral oncogene homolog (avian), and cyclin-dependent kinase 6) were reduced (p < 0.05) in placentas with low maternal folate status. Conclusion This study supports that placental dysfunction contributes to impaired fetal growth in women with low folate status and suggests altered placental expression of folate-sensitive miRNAs and target genes as a mechanistic link.

Details

Original languageEnglish
Article number1600646
JournalMolecular Nutrition & Food Research
Volume61
Issue number8
Early online date21 Mar 2017
Publication statusPublished - Aug 2017

Keywords

  • fetal growth, folate deficiency, gene expression, microRNA, placental dysfunction