Systematic Review of Micro-RNA Expression in Pre-Eclampsia Identifies a Number of Common Pathways Associated with the Disease

Abstract

BackgroundPre-eclampsia (PE) is a complex, multi-systemic condition of pregnancy which greatly impacts maternal and perinatal morbidity and mortality. MicroRNAs (miRs) are differentially expressed in PE and may be important in helping to understand the condition and its pathogenesis.MethodsCase-control studies investigating expression of miRs in PE were collected through a systematic literature search. Data was extracted and compared from 58 studies to identify the most promising miRs associated with PE pathogenesis and identify areas of methodology which could account for often conflicting results.ResultsSome of the most frequently differentially expressed miRs in PE include miR-210, miR-223 and miR-126/126* which associate strongly with the etiological domains of hypoxia, immunology and angiogenesis. Members of the miR-515 family belonging to the imprinted chromosome 19 miR cluster with putative roles in trophoblast invasion were also found to be differentially expressed. Certain miRs appear to associate with more severe forms of PE such as miR-210 and the immune-related miR-181a and miR-15 families. Patterns of miR expression may help pinpoint key pathways (e.g. IL-6/miR-223/STAT3) and aid in untangling the heterogeneous nature of PE. The detectable presence of many PE-associated miRs in antenatal circulatory samples suggests their usefulness as predictive biomarkers. Further progress in ascertaining the clinical value of miRs and in understanding how they might contribute to pathogenesis is predicated upon resolving current methodological challenges in studies. These include differences in diagnostic criteria, cohort characteristics, sampling technique, RNA isolation and platform-dependent variation in miR profiling.ConclusionReviewing studies of PE-associated miRs has revealed their potential as informants of underlying target genes and pathways relating to PE pathogenesis. However, the incongruity in results across current studies hampers their capacity to be useful biomarkers of the condition.

The TGFβ Family in Human Placental Development at the Fetal-Maternal Interface

“…Expression analysis in placentae from PE women has shown reduced expression of members of the BMP signaling pathway (ALK1, ID1, and EGFL7) [95,104,118]. Together with the known sFLT1 and sENG biomarkers of PE, the molecular mechanism is narrowed down to the BMP signaling pathway and possible cross-talk with VEGF and NOTCH signaling.…”

Relationship Between Fetal Sex and the Expression Levels of Micrornas in Healthy Pregnancies

“…MikroRNA'lar (miRNA), 19-25 nükleotid uzunluğunda, kodlamayan, hedefleri olan mRNA'lara bağlanarak yıkımında rol oynayan ve tranlasyonu baskılayarak gen ifadesinin düzenlenmesinde görev alan küçük fonksiyonel RNA molekülleridir (1,2). Günümüzde, maternal kandaki miRNA düzeyleri ile gebeliğe özgü preeklampsi, gestasyonel diyabet (GDM) gibi çeşitli patolojiler arasındaki ilişkileri araştıran çok sayıda çalışma mevcuttur (3)(4)(5)(6)(7)(8). Maternal dolaşıma sinsityotrofoblastlardan ekzozomlar yoluyla plasental kökenli miRNA'ların salındığı belirlenmiş ve bunların tanıda önem taşıdığına dikkat çekilmiştir (7,8).…”

Exploration of the regulation and control mechanisms of miR‑145 in trophoblast cell proliferation and invasion

“…Previous studies have demonstrated that PE is a common and severe health problem for fetuses and expectant women, a leading cause of maternal and fetal mortality and morbidity (5). PE is associated with fetus maldevelopment and may lead to eclampsia and even miscarriage (5)(6)(7). Worldwide, there are ~55,000 deaths associated with PE reported annually (7), and the underlying cause of PE remains unknown.…”