Expression profiles and functions of ferroptosis-related genes in the placental tissue samples of early- and late-onset preeclampsia patients

BMC Pregnancy Childbirth. 2022 Jan 31;22(1):87. doi: 10.1186/s12884-022-04423-6.

Abstract

Background: The accumulation of reactive oxygen species (ROS) resulting from upregulated levels of oxidative stress is commonly implicated in preeclampsia (PE). Ferroptosis is a novel form of iron-dependent cell death instigated by lipid peroxidation that likely plays an important role in PE pathogenesis. This study aimed to investigate the expression profiles and functions of ferroptosis-related genes (FRGs) in early-onset preeclampsia (EOPE) and late-onset preeclampsia (LOPE).

Methods: Gene expression data and clinical information were downloaded from the Gene Expression Omnibus (GEO) database. The "limma" R package was used to screen differentially expressed genes. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein-protein interaction (PPI) network analyses were conducted to investigate the bioinformatics functions and molecular interactions of significantly different FRGs. Quantitative reverse transcription polymerase chain reaction (RT-qPCR) was used to verify the expression of hub FRGs in PE.

Results: A total of 4215 differentially expressed genes (DEGs) were identified between EOPE and preterm cases while 556 DEGs were found between LOPE and term controls. Twenty significantly different FRGs were identified in EOPE subtypes, while only 3 FRGs were identified in LOPE subtypes. Functional enrichment analysis revealed that the differentially expressed FRGs were mainly involved in EOPE and enriched in hypoxia- and iron-related pathways, such as the response to hypoxia, iron homeostasis and iron ion binding process. PPI network analysis and verification by RT-qPCR resulted in the identification of the following five FRGs of interest: FTH1, HIF1A, FTL, MAPK8 and PLIN2.

Conclusions: EOPE and LOPE have distinct underlying molecular mechanisms, and ferroptosis may be mainly implicated in the pathogenesis of EOPE. Further studies are necessary for deeper inquiry into placental ferroptosis and its role in the pathogenesis of EOPE.

Keywords: Bioinformatics; Early-onset preeclampsia; Ferroptosis; Preeclampsia.

MeSH terms

  • Adult
  • Apoferritins / genetics
  • Down-Regulation
  • Female
  • Ferritins / genetics
  • Ferroptosis / genetics*
  • Gene Expression Profiling*
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Mitogen-Activated Protein Kinase 8 / genetics
  • Oxidoreductases / genetics
  • Perilipin-2 / genetics
  • Placenta / metabolism
  • Pre-Eclampsia / genetics*
  • Pregnancy
  • Pregnancy Trimesters / metabolism
  • Principal Component Analysis
  • Protein Interaction Maps
  • Reverse Transcriptase Polymerase Chain Reaction
  • Up-Regulation

Substances

  • FTL protein, human
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • PLIN2 protein, human
  • Perilipin-2
  • Ferritins
  • Apoferritins
  • FTH1 protein, human
  • Oxidoreductases
  • Mitogen-Activated Protein Kinase 8