Abstract
Preeclampsia is a multisystem disease that significantly contributes to maternal and foetal morbidity and mortality. In this study, we used a nonbiased microarray approach to identify novel circulating miRNAs in maternal plasma that may be associated with preeclampsia. Plasma samples were obtained at 16 and 28 weeks of gestation from 18 women who later developed preeclampsia (cases) and 18 matched women with normotensive pregnancies (controls). We studied miRNA expression profiles in plasma and subsequently confirmed miRNA and target gene expression in placenta samples. Placental samples were obtained from an independent cohort of 19 women with preeclampsia matched with 19 women with normotensive pregnancies. From the microarray, we identified one miRNA that was significantly differentially expressed between cases and controls at 16 weeks of gestation and six miRNAs that were significantly differentially expressed at 28 weeks. Following qPCR validation, only one miR-206 was found to be significantly increased in 28-week samples in women who later developed preeclampsia (1.4-fold change ± 0.2). The trend for increase in miR-206 expression was mirrored within placental tissue from women with preeclampsia. In parallel, IGF-1, a target gene of miR-206, was also found to be downregulated (0.41 ± 0.04) in placental tissue from women with preeclampsia. miR-206 expression was also detectable in myometrium tissue and trophoblast cell lines. Our pilot study has identified miRNA-206 as a novel factor upregulated in preeclampsia within the maternal circulation and in placental tissue.
Highlights
Preeclampsia is a syndrome that occurs during the second half of pregnancy in approximately 1–5% of women in the developed world [1]
Following quantitative PCR (qPCR) validation, only one miR-206 was found to be significantly increased in 28-week samples in women who later developed preeclampsia (1.4-fold change Æ 0.2)
insulin-like growth factor 1 (IGF-1), a target gene of miR-206, was found to be downregulated (0.41 Æ 0.04) in placental tissue from women with preeclampsia. miR-206 expression was detectable in myometrium tissue and trophoblast cell lines
Summary
Preeclampsia is a syndrome that occurs during the second half of pregnancy in approximately 1–5% of women in the developed world [1]. MiRNAs have been shown to play a functional role in physiological processes important in pregnancy such as placental development, trophoblast proliferation and migration and angiogenesis [2]. The origin of circulating miRNAs is not fully understood and it is not known how their levels are altered in disease, or if they have a particular target via which they can exert a functional role. Circulating miRNAs are protected from degradation by specific proteins [3,4] within exosomes [5] or microparticles [6]. This suggests that miRNA in plasma may serve an important role requiring their integrity to be preserved. Few studies into preeclampsia have assessed levels of circulating miRNAs in the plasma and have either focused on late gestation or have lacked translation into relevant tissues [7,8,9]
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