Circulating MicroRNAs in the Second Trimester From Pregnant Women Who Subsequently Developed Preeclampsia: Potential Candidates as Predictive Biomarkers and Pathway Analysis for Target Genes of miR-204-5p

Abstract

MicroRNAs (miRNAs) play an important role in the pathophysiology of preeclampsia (PE). However, the expression of circulating miRNAs was not analyzed in the second trimester of pregnancy, a period of major relevance to identify predictive biomarkers for PE. Therefore, we examined the expression profiles of 84 circulating miRNAs using a PCR array in plasma collected between 20 and 25 weeks of gestation from pregnant women, who subsequently developed PE and those who remained healthy during pregnancy, randomly selected from a prospective cohort. Overall, 23 miRNAs had a fold change > 2.0 and were considered to be upregulated in plasma from pregnant women who subsequently developed PE, even before the onset of clinical symptoms of PE. However, only miR-204-5p was statistically significant (P = 0.0082). Experimentally validated interactions for the target genes of miR-204-5p extracted from miRTarBase were used in the gene set functional enrichment analysis to identify Reactome pathways. The network connecting the 37 target genes for miR-204-5p revealed pathways of known pathophysiological relevance during the early development of PE and included key genes related to PE, such as BDNF, MMP-9, MALAT1, TGFBR2, and SIRT1. We further depicted downstream targets of SIRT1 that are related to the vascular endothelial function or implicated in the pathophysiology of PE, namely, FOXO1, NFκB, HIF-1α, NOS3, and PPAR-γ. Our novel findings provide for circulating miRNAs upregulated in the second trimester on plasma from pregnant women who subsequently developed PE that is potentially related to the early development of PE, which may guide further studies focused on the validation of potential predictive biomarkers in PE.

Systematic Review of the Diagnostic and Clinical Utility of Salivary microRNAs in Traumatic Brain Injury (TBI)

“…As such, the evaluation of miRNA biomarker variability in heterogeneous or comorbid populations is a challenge. For example, the studies of this review included a mix of male and female subjects, however sex-based differences may influence miRNA expression [ 55 ] including the regulation of gonadal hormones [ 56 ], menstrual cycles [ 57 ] and pregnancy [ 58 ]. The diet of subjects may also affect miRNA expression by contributing external miRNAs that are indistinguishable from endogenous miRNAs [ 59 ].…”

A prospective study of the proteome of equine pre‐implantation embryo

“…Similarly, analysis of embryo culture media from IVF programs showed a reduced expression of hsa‐mir‐20a‐5p in samples from low quality embryos (Abu‐Halima et al., 2020). The use of miRNA as reproductive biomarkers brings new possibilities for non‐invasive predictors, like hsa‐mir‐103a‐3p, which showed higher expression in plasma from pregnant women with severe preeclampsia (Luizon et al., 2021). Moreover, miR‐10a‐5p modulates BDNF expression in human follicular fluid and could indicate embryo quality on days 3 and 5, potentially aiding embryo selection and IVF success rates (Zhang, Su, et al., ; Zhang, Zhang, et al., 2021).…”

Circulating microRNAs as Reliable Tumor Biomarkers: Opportunities and Challenges Facing Clinical Application

“…Several studies have reported an effect of gonadal steroids on miRNAs expression (Morgan & Bale, 2012). Menstrual cycles and pregnancy are among the events that also have an effect on total circulating miRNA profiles (Rekker et al, 2013;Luizon et al, 2021).…”