Abstract
BackgroundThe 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).MethodsGene 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.ResultsA 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.ConclusionsEOPE 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.
Highlights
The accumulation of reactive oxygen species (ROS) resulting from upregulated levels of oxidative stress is commonly implicated in preeclampsia (PE)
For the first time, that many key proteins implicated in the regulation of ferroptosis were aberrantly expressed in the placental tissues of patients with early-onset preeclampsia (EOPE), but few were aberrantly expressed in the placental tissues of patients with late-onset preeclampsia (LOPE)
Expressed genes in the placentas of patients with PE and PE subtypes The microarray expression in placental tissues from patients with EOPE, LOPE, and preterm and at term controls was downloaded from dataset GSE74341 in the Gene Expression Omnibus (GEO) database (Fig. 1A)
Summary
The accumulation of reactive oxygen species (ROS) resulting from upregulated levels of oxidative stress is commonly implicated in preeclampsia (PE). Yang et al BMC Pregnancy and Childbirth (2022) 22:87 It occurs in 5–7% of pregnancies and is a leading cause of maternal and perinatal mortality [1]. PE can be classified into two categories by the time of onset of clinical signs and symptoms [2, 3]: early-onset preeclampsia (EOPE, < 34 weeks of gestation) and late-onset preeclampsia (LOPE, ≥34 weeks of gestation). It is widely accepted that EOPE is mainly due to abnormal implantation and placentation in early gestation, whereas LOPE commonly results from placental dysfunction caused by maternal disease [4]. Stage 1 is composed of abnormal implantation and malplacentation, while stage 2 is the clinical syndrome that results from the release of factors by a dysfunctional placenta. Oxidative stress is proposed to be implicated in the clinical manifestations of PE, the underlying mechanism remains largely unknown
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