The aim of the study was to verify if quantification of placental specific C19MC microRNAs in plasma exosomes would be able to differentiate during the early stages of gestation between patients subsequently developing pregnancy-related complications and women with the normal course of gestation and if this differentiation would lead to the improvement of the diagnostical potential. The retrospective study on singleton Caucasian pregnancies was performed within 6/2011-2/2019. The case control study, nested in a cohort, involved women that later developed GH (n = 57), PE (n = 43), FGR (n = 63), and 102 controls. Maternal plasma exosome profiling was performed with the selection of C19MC microRNAs with diagnostical potential only (miR-516b-5p, miR-517-5p, miR-518b, miR-520a-5p, miR-520h, and miR-525-5p) using real-time RT-PCR. The down-regulation of miR-517-5p, miR-520a-5p, and miR-525-5p was observed in patients with later occurrence of GH and PE. Maternal plasma exosomal profiling of selected C19MC microRNAs also revealed a novel down-regulated biomarker during the first trimester of gestation (miR-520a-5p) for women destinated to develop FGR. First trimester circulating plasma exosomes possess the identical C19MC microRNA expression profile as placental tissues derived from patients with GH, PE and FGR after labor. The predictive accuracy of first trimester C19MC microRNA screening (miR-517-5p, miR-520a-5p, and miR-525-5p) for the diagnosis of GH and PE was significantly higher in the case of expression profiling of maternal plasma exosomes compared to expression profiling of the whole maternal plasma samples.

• Klíčová slova
• C19MC microRNA, exosomes, expression, fetal growth restriction, gestational hypertension, plasma, prediction, preeclampsia, pregnancy-related complications, screening,
• MeSH
• biologické markery MeSH
• cirkulující mikroRNA * MeSH
• exozómy * metabolismus   MeSH
• hypertenze indukovaná těhotenstvím krev   diagnóza   MeSH
• lidé MeSH
• preeklampsie krev   diagnóza   MeSH
• prognóza MeSH
• první trimestr těhotenství MeSH
• ROC křivka MeSH
• růstová retardace plodu krev   diagnóza   MeSH
• těhotenství MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• biologické markery MeSH
• cirkulující mikroRNA * MeSH

OBJECTIVES: A nested case control study of a longitudinal cohort comparing pregnant women enrolled at 10 to 13 gestational weeks was carried out to evaluate risk assessment for preeclampsia and IUGR based on circulating placental specific C19MC microRNAs in early pregnancy. METHODS: The expression of placental specific C19MC microRNAs (miR-516b-5p, miR-517-5p, miR-518b, miR-520a-5p, miR-520h, and miR-525-5p) was determined in plasma samples from pregnancies that subsequently developed preeclampsia (n = 21), IUGR (n = 18), and 58 normal pregnancies using real-time PCR and comparative Ct method relative to synthetic Caenorhabditis elegans microRNA (cel-miR-39). RESULTS: Circulating C19MC microRNAs were up-regulated (miR-517-5p, p = 0.005; miR-518b, p = 0.013; miR-520h, p = 0.021) or showed a trend toward up-regulation in patients destined to develop preeclampsia (miR-520a-5p, p = 0.067; miR-525-5p, p = 0.073). MiR-517-5p had the best predictive performance for preeclampsia with a sensitivity of 42.9%, a specificity of 86.2%, a PPV of 52.9% and a NPV of 80.6%. The combination of all examined circulating C19MC microRNAs had no advantage over using only the miR-517-5p biomarker to predict the occurrence of preeclampsia (a sensitivity of 20.6%, a specificity of 90.8%, a PPV of 44.8%, and a NPV of 76.0%). CONCLUSIONS: Up-regulation of miR-517-5p, miR-518b and miR-520h was associated with a risk of later development of preeclampsia. First trimester screening of extracellular miR-517-5p identified a proportion of women with subsequent preeclampsia. No circulating C19MC microRNA biomarkers were identified that could predict later occurrence of IUGR.

• MeSH
• biologické markery krev   MeSH
• dospělí MeSH
• lidé MeSH
• mikro RNA krev   MeSH
• prediktivní hodnota testů MeSH
• preeklampsie krev   diagnóza   MeSH
• prenatální diagnóza metody   MeSH
• první trimestr těhotenství krev   MeSH
• růstová retardace plodu krev   diagnóza   MeSH
• stanovení celkové genové exprese MeSH
• studie případů a kontrol MeSH
• těhotenství MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• biologické markery MeSH
• mikro RNA MeSH