From diverging reports to differing phenotypes: Are microRNAs indicative of preeclampsia subtypes?

Abstract

Objective: The aim of this project was to clarify if there is an alteration in the expression profiles of five miRNAs (miR-1, miR-181a, miR-195, miR-210 and miR-584) in preeclamptic placentas versus normal placentas.

Experimental design: Formalin-fixed and paraffin-embedded placental samples from pregnancies complicated with preeclampsia (n=12) and from healthy pregnancies (n=10) were used in this study. The preeclampsia cases were all considered to be of early-onset (≤34 weeks of gestation) and five were considered to be severe. The assessment of relative miRNA quantities was performed by two-step quantitative reverse transcription polymerase chain reaction.

Results: Three of the analysed placental miRNAs were revealed to be significantly under-expressed in preeclampsia (miR-1, miR-210 and miR-584). miR-195 did not show any significant change and miR-181a was not successfully assessed. Notably, the significance probability obtained for miR-1 when removing the severe cases from the statistical analysis dropped radically (from p-value=0.036 to p-value=0.002), in spite of the reduction in sample size. The result obtained for miR-210 contrasts with most published studies, performed in severe preeclampsia cases; but it is in concordance with the one study that performed this analysis in mild cases. miR-584 remained very significantly under-expressed whether severe samples were included or excluded from the analysis.

Conclusion: The results lead us to conclude that miR-1, miR-210 and miR-584 are under-expressed in preeclamptic placentas. While some mechanisms appear to be common to preeclampsia as a whole (in this case, reflected by miR-584), some molecules seem to be specific for given subtypes of the syndrome (namely, miR-1 and miR-210). In addition, the widespread assumption that early preeclampsia is more severe is challenged by these results, which indicate different miRNA profiles within early cases of the syndrome. All in all, it seems that miRNA analysis can provide indication about the preeclamptic phenotype, and may provide further insight into the pathophysiology of preeclampsia and its distinct varieties.