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.

• Keywords
• C19MC microRNA, exosomes, expression, fetal growth restriction, gestational hypertension, plasma, prediction, preeclampsia, pregnancy-related complications, screening,
• MeSH
• Biomarkers MeSH
• Circulating MicroRNA * MeSH
• Exosomes * metabolism   MeSH
• Hypertension, Pregnancy-Induced blood   diagnosis   MeSH
• Humans MeSH
• Pre-Eclampsia blood   diagnosis   MeSH
• Prognosis MeSH
• Pregnancy Trimester, First MeSH
• ROC Curve MeSH
• Fetal Growth Retardation blood   diagnosis   MeSH
• Pregnancy MeSH
• Check Tag
• Humans MeSH
• Pregnancy MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Biomarkers MeSH
• Circulating MicroRNA * 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
• Biomarkers blood   MeSH
• Adult MeSH
• Humans MeSH
• MicroRNAs blood   MeSH
• Predictive Value of Tests MeSH
• Pre-Eclampsia blood   diagnosis   MeSH
• Prenatal Diagnosis methods   MeSH
• Pregnancy Trimester, First blood   MeSH
• Fetal Growth Retardation blood   diagnosis   MeSH
• Gene Expression Profiling MeSH
• Case-Control Studies MeSH
• Pregnancy MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Pregnancy MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Biomarkers MeSH
• MicroRNAs MeSH

To demonstrate that pregnancy-related complications are associated with alterations in placental microRNA expression. Gene expression of 15 C19MC microRNAs (miR-512-5p, miR-515-5p, miR-516-5p, miR-517-5p, miR-518b, miR-518f-5p, miR-519a, miR-519d, miR-519e-5p, miR-520a-5p, miR-520h, miR-524-5p, miR-525, miR-526a, and miR-526b) was assessed in placental tissues, compared between groups (21 gestational hypertension [GH], 63 preeclampsia, 36 fetal growth restriction [FGR], and 42 normal pregnancies), and correlated with the severity of the disease with respect to clinical signs, delivery date, and Doppler ultrasound parameters. The expression profile of microRNAs was different between pregnancy-related complications and controls. The downregulation of 4 of 15 (miR-517-5p, miR-519d, miR-520a-5p, and miR-525), 6 of 15 (miR-517-5p, miR-518f-5p, miR-519a, miR-519d, miR-520a-5p, and miR-525), and 11 of 15 (miR-515-5p, miR-517-5p, miR-518b, miR-518f-5p, miR-519a, miR-519d, miR-520a-5p, miR-520h, miR-524-5p, miR-525, and miR-526a) microRNAs was associated with GH, FGR, and preeclampsia, respectively. Sudden onset of severe preeclampsia requiring immediate termination of gestation and mild forms of preeclampsia (persisting for several weeks) were associated with similar microRNA expression profile (downregulation of miR-517-5p, miR-520a-5p, miR-524-5p, and miR-525). In addition, miR-519a was found to be associated with severe preeclampsia. The longer the pregnancy-related disorder lasted, the more extensive was the downregulation of microRNAs (miR-515-5p, miR-518b, miR-518f-5p, miR-519d, and miR-520h). The downregulation of some C19MC microRNAs is a common phenomenon shared between GH, preeclampsia, and FGR. On the other hand, some of the C19MC microRNAs are only downregulated just in preeclampsia.

• MeSH
• Biomarkers metabolism   MeSH
• Adult MeSH
• Hypertension, Pregnancy-Induced metabolism   MeSH
• Humans MeSH
• Chromosomes, Human, Pair 19 genetics   MeSH
• MicroRNAs genetics   metabolism   MeSH
• Young Adult MeSH
• Multigene Family MeSH
• Placenta metabolism   MeSH
• Pre-Eclampsia metabolism   MeSH
• Retrospective Studies MeSH
• Fetal Growth Retardation metabolism   MeSH
• Pregnancy MeSH
• Transcriptome MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Pregnancy MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Biomarkers MeSH
• MicroRNAs MeSH

OBJECTIVE: The objective of the study was to evaluate risk assessment for gestational hypertension based on the profile of circulating placental specific C19MC microRNAs in early pregnancy. STUDY DESIGN: The prospective longitudinal cohort study of women enrolled at first trimester screening at 10 to 13 weeks was carried out (n = 267). Relative quantification of placental specific C19MC microRNAs (miR-516-5p, miR-517*, miR-518b, miR-520a*, miR-520h, miR-525 and miR-526a) was determined in 28 normal pregnancies and 18 pregnancies which developed gestational hypertension using real-time PCR and a comparative Ct method relative to synthetic C. elegans microRNA (cel-miR-39). RESULTS: Increased extracellular C19MC microRNA plasmatic levels (miR-516-5p, p<0.001; miR-517*, p = 0.007; miR-520h, p<0.001; miR-518b, p = 0.002) were detected in patients destined to develop gestational hypertension. MiR-520h had the best predictive performance with a PPV of 84.6% at a 7.1% false positive rate. The combination of miR-520h and miR-518b was able to predict 82.6% of women at the same false positive rate. The overall predictive capacity of single miR-518b (73.3% at 14.3% FPR), miR-516-5p (70.6% at 17.9% FPR) and miR-517* (57.9% at 28.6% FPR) biomarkers was lower. CONCLUSION: The study brought interesting finding that the up-regulation of miR-516-5p, miR-517*, miR-520h and miR-518b is associated with a risk of later development of gestational hypertension. First trimester screening of extracellular miR-520h alone or in combination with miR-518b identified a significant proportion of women with subsequent gestational hypertension.

• MeSH
• Caenorhabditis elegans MeSH
• Hypertension, Pregnancy-Induced blood   genetics   pathology   MeSH
• Humans MeSH
• Chromosomes, Human, Pair 19 MeSH
• MicroRNAs blood   genetics   MeSH
• Placenta pathology   MeSH
• Prospective Studies MeSH
• Pregnancy Trimester, First MeSH
• Base Sequence MeSH
• Pregnancy MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Pregnancy MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• MicroRNAs MeSH