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Detection of extracellular microRNAs in maternal circulation - diagnosis and prognosis of pregnancy related complications
Ondráčková, Markéta ; Hromadníková, Ilona (advisor) ; Daňková, Pavlína (referee)
MicroRNAs (miRNAs) are small noncoding RNAs of length 18 to 25 nucleotides that regulate gene expression posttranscriptionally. Expression of some miRNAs is tissue specific. I assumed that pregnancy induced complications associated with placental insufficiency could be characterized by a unique profil of placental-specific miRNAs in maternal circulation. I measured concentration and gene expression of selected miRNAs (miR-516-5p, miR-517*, miR-518b, miR-520a*, miR-520h, miR-525 and miR-526a) in the plasma of patients with preeclampsia (PE), fetal growth restriction (FGR) and gestational hypertension (GH). The control group consisted of patients with a normal course of pregnancy (FG). I processed 168 plasma samples, the representation of individual diagnosis were as follows: PE 63, FGR 27, GH 23, FG 55. Detection and quantification was carried out by quantitative real-time PCR. I identified three miRNAs with elevated levels in a group of preeclamptic patients: miR-517*, miR-520a* and miR-525. The severity of the PE, which was characterized by a form of the disease (mild or severe PE) and term (before or after the 34th week of pregnancy), did not have a statistically significant effect on the levels of miRNAs. More than a quarter of patients had PE superimposed on previous hypertension. Previous history of...
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Markers for the prediction of preeclampsia and their relevance in the first trimester of pregnancy
Šedová, Lenka ; Kestlerová, Andrea (advisor) ; Švandová, Ivana (referee)
Preelampsia is a clinical syndrome found uniquely in a pregnant patient with an incidence 2 - 8 % of pregnancies worldwide. It is defined as the new onset of hypertension and proteinuria after 20 weeks of gestation, resolving with delivery or soon thereafter. Its worst consequences are eclampsia with tonic and clonic seizures and possibly coma. Also pulmonary edema, CNS hemorrhage, anaemia, hepatorenal failure, circulation failure and other complications can occur. In its most severe form, it affects nearly every organ. Preeclampsia remains a major cause of premature delivery and both maternal and neonatal mortality and morbidity. The origin and the cause of the disease remain unknown and therefore the medical treatment focuses only on clinical manifestations. Timely prediction of preeclampsia would enable accurate therapeutic treatment and a decrease of the threat to maternal and fetal health. In this study, the most important predictive biomarkers of PE and their relevance in the first trimester of gestation are presented. Furthermore, a first trimester screening with the best prediction rates is described. Powered by TCPDF (www.tcpdf.org)
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Postpartal expression profile of cardiovascular microRNAs with regard to occurrence of pregnancy-related complications - study on mothers 3-10 years after the delivery
Marvanová, Veronika ; Hromadníková, Ilona (advisor) ; Korabečná, Marie (referee)
The aim of this study was to investigate gene expression of cardiovascular miRNAs in peripheral blood of mothers after delivery. MiRNAs are small non-coding RNAs, which significantly modulate posttranscriptional adjustments of mRNA and thus regulate gene expression across biological processess. Dysregulation of miRNAs is associated with many pathological phenomena, thanks that we can use them for diagnosis and potentionaly we can treat these diseases by the manipulation of miRNA gene expression. We examined gene expression of circulating miRNAs associated with cardiovascular diseases, and we investigated, how the expression profile depends on pregnancy course and manifestation of pregnancy-related complications. For this purpose we examined material from 221 mothers 3-10 years after delivery. A group with identical pregnancy-related complication was always compared with a group of mothers after physiological pregnancy. Gene expression of 29 cardiovascular miRNAs in peripheral blood was studied using reverse transcription and quantitative real-time PCR. It was confirmed, that the expression profile of miRNAs differed between pregnancy-related complications and physiological controls. We also confirmed, that the profile of gene expression discovered at mothers 3-10 years after delivery was different...
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Postnatal screening of cardiovascular microRNAs in children descending from pregnancy-related complications
Semencová, Andrea ; Hromadníková, Ilona (advisor) ; Korabečná, Marie (referee)
Children descending from pregnancy complicated by gestational hypertension, preeclampsia or fetal growth restriction have a lifelong increased risk of development of cardiovascular disease. This study investigates the expression profile of 29 cardiovascular and cerebrovascular microRNAs in children at the age of 3 to 11 years. MicroRNAs are short non-coding RNA molecules affecting gene expression by posttranscriptional modifications of mRNA, which affects biological processes. Abnormal microRNA levels can lead to pathological conditions of the individual. This study explores the relationship between dysregulated microRNA levels in whole peripheral venous blood of children and the presence of complications during pregnancy. Furthermore, this study looks at expression profile specificities depending on the presence of pathology in the child's cardiovascular system, as found in a clinical examination consisting of BMI assessment and evaluation, blood pressure testing and ultrasound examination of the heart. Dysregulated profile was present in children with gestational hypertension in miR-1-3p, miR-17-5p, miR-20a-5p, miR-21-5p, miR-26a-5p, miR-29a-3p, miR-126-3p, miR-133a-3p, miR-181a-5p, miR-199a-5p, miR-342-3p and miR-499-5p. In children with preeclampsia, dysregulation was found with miR-1-3p and...
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First-trimester screening of pregnancy-related complications using plasma exosomal C19MC microRNAs
Špačková, Kamila ; Hromadníková, Ilona (advisor) ; Daňková, Pavlína (referee)
Pregnancy-related complications such as gestational hypertension, preeclampsia, fetal growth restriction, gestational diabetes mellitus, spontaneous preterm birth, and preterm premature rupture of membranes may have severe consequences for both the mother and the child. The development of reliable early screening methods for pregnancy-related complications has therefore been a long-term goal of obstetrics. New possibilities for prenatal diagnostics have opened with the discovery of circulating microRNAs in maternal plasma. MicroRNAs are short, noncoding, 21 to 23 nucleotides long, single-strand RNAs whose main function is to regulate gene expression. During pregnancy, both common and unique miRNAs are expressed by the placenta, amongst them the miRNAs of the C19MC cluster. Several C19MC miRNAs have been shown to display a different expression profile associated with certain pregnancy-related complications. This thesis identifies the plasma exosomal profiles of six C19MC miRNAs (miR-516-5p, miR-517-5p, miR-518b, miR-520a-5p, miR-520h, and miR-525-5p) in patients in their first trimester of gestation who later developed pregnancy-related complications, and compares them with profiles in patients with normal pregnancies.
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Postpartal expression profile of cardiovascular microRNAs with regard to occurrence of pregnancy-related complications - study on mothers 3-10 years after the delivery
Marvanová, Veronika ; Hromadníková, Ilona (advisor) ; Korabečná, Marie (referee)
The aim of this study was to investigate gene expression of cardiovascular miRNAs in peripheral blood of mothers after delivery. MiRNAs are small non-coding RNAs, which significantly modulate posttranscriptional adjustments of mRNA and thus regulate gene expression across biological processess. Dysregulation of miRNAs is associated with many pathological phenomena, thanks that we can use them for diagnosis and potentionaly we can treat these diseases by the manipulation of miRNA gene expression. We examined gene expression of circulating miRNAs associated with cardiovascular diseases, and we investigated, how the expression profile depends on pregnancy course and manifestation of pregnancy-related complications. For this purpose we examined material from 221 mothers 3-10 years after delivery. A group with identical pregnancy-related complication was always compared with a group of mothers after physiological pregnancy. Gene expression of 29 cardiovascular miRNAs in peripheral blood was studied using reverse transcription and quantitative real-time PCR. It was confirmed, that the expression profile of miRNAs differed between pregnancy-related complications and physiological controls. We also confirmed, that the profile of gene expression discovered at mothers 3-10 years after delivery was different...
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The expression profile of cardiovascular disease associated microRNAs in pregnancies with clinical manifestation of gestational hypertension, preeclampsia and intrauterine growth restriction
Bohatá, Jana ; Hromadníková, Ilona (advisor) ; Korabečná, Marie (referee)
MicroRNA (miRNA) are small non-coding 21-23 nucleotides long one strand RNAs. They are among the major posttranscriptional regulators of gene expression that regulate both physiological and pathological processes. Some of microRNAs, amount of their expression respectively, are specific only for certain type of tissue or pathological condition. The hypothesis for my diploma thesis was that gene expression of 28 cardiovascular disease associated microRNAs (miR-1-3p, miR-16-5p, miR-17-5p, miR- 20a-5p, miR-20b-5p, miR-21-5p, miR-23a-3p, miR-24-3p, miR-26a-5p, miR-29a-3p, miR-92a-3p, miR-100-5p, miR-103a-3p, miR-125b-5p, miR-126-3p, miR-130b-3p, miR-133a-3p, miR-143-3p, miR-145-5p, miR-146a-5p, miR-181-5p, miR-195-5p, miR- 199a-5p, miR-210-3p, miR-221-3p, miR-342-3p, miR-499a-5p, miR-574-3p) would differ in umbilical cord blood between groups of women with physiological pregnancies (FG), gestational hypertension (GH), preeclampsia (PE) and fetal growth restriciton (FGR). The studied cohort consisted of 184 pregnant women involving 44 controls, 47 GH pregnancies, 56 PE pregnancies and 37 FGR pregnancies. Relative quantification of microRNAs was performed by quantitative real-time PCR. Results showed a trend to miR-195-5p down-regulation in umbilical cord blood of GH patients. On the other hand, mild PE...
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Markers for the prediction of preeclampsia and their relevance in the first trimester of pregnancy
Šedová, Lenka ; Kestlerová, Andrea (advisor) ; Švandová, Ivana (referee)
Preelampsia is a clinical syndrome found uniquely in a pregnant patient with an incidence 2 - 8 % of pregnancies worldwide. It is defined as the new onset of hypertension and proteinuria after 20 weeks of gestation, resolving with delivery or soon thereafter. Its worst consequences are eclampsia with tonic and clonic seizures and possibly coma. Also pulmonary edema, CNS hemorrhage, anaemia, hepatorenal failure, circulation failure and other complications can occur. In its most severe form, it affects nearly every organ. Preeclampsia remains a major cause of premature delivery and both maternal and neonatal mortality and morbidity. The origin and the cause of the disease remain unknown and therefore the medical treatment focuses only on clinical manifestations. Timely prediction of preeclampsia would enable accurate therapeutic treatment and a decrease of the threat to maternal and fetal health. In this study, the most important predictive biomarkers of PE and their relevance in the first trimester of gestation are presented. Furthermore, a first trimester screening with the best prediction rates is described. Powered by TCPDF (www.tcpdf.org)
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The Role of Heat Shock Proteins in Pathogenesis of Placental Insufficinecy
Slabá, Kristýna ; Hromadníková, Ilona (advisor) ; Černý, Jan (referee)
Heat shock proteins (Hsp) are highly conserved proteins that are part of the universal stress response of the cell. Their main function is to protect cells against structural and functional damage. Organisms exposed to different forms of stress, such as e.g. a lack of nutrients or water, hypoxia, infection or inflammation, demonstrated an increased gene expression of these proteins. Pregnancy complications cause stress conditions for maternal and fetal organism, which may result in an increased gene expression of Hsp. In my thesis, I examined the concentration of extracellular mRNA for five different heat shock proteins (Hsp27, Hsp60, Hsp70, Hsp90, HspBP1) in the plasma of pregnant women and wheather this concentration is affected by possible pregnancy complications (preeclampsia, fetal growth restriction and gestational hypertension). I also investigated a possible correlation between mRNA plasma concentration for Hsp and pulsatility index values (PI) obtained by Doppler ultrasound. This research should help to invent a new predictive method for pregnancy complications, based on a detection of specific biomarkers in the first trimester of pregnancy. The research was conducted on plasma samples obtained from peripheral blood of pregnant women, whose collection was performed during clinical manifestations of...
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Detection of extracellular microRNAs in maternal circulation - diagnosis and prognosis of pregnancy related complications
Ondráčková, Markéta ; Hromadníková, Ilona (advisor) ; Daňková, Pavlína (referee)
MicroRNAs (miRNAs) are small noncoding RNAs of length 18 to 25 nucleotides that regulate gene expression posttranscriptionally. Expression of some miRNAs is tissue specific. I assumed that pregnancy induced complications associated with placental insufficiency could be characterized by a unique profil of placental-specific miRNAs in maternal circulation. I measured concentration and gene expression of selected miRNAs (miR-516-5p, miR-517*, miR-518b, miR-520a*, miR-520h, miR-525 and miR-526a) in the plasma of patients with preeclampsia (PE), fetal growth restriction (FGR) and gestational hypertension (GH). The control group consisted of patients with a normal course of pregnancy (FG). I processed 168 plasma samples, the representation of individual diagnosis were as follows: PE 63, FGR 27, GH 23, FG 55. Detection and quantification was carried out by quantitative real-time PCR. I identified three miRNAs with elevated levels in a group of preeclamptic patients: miR-517*, miR-520a* and miR-525. The severity of the PE, which was characterized by a form of the disease (mild or severe PE) and term (before or after the 34th week of pregnancy), did not have a statistically significant effect on the levels of miRNAs. More than a quarter of patients had PE superimposed on previous hypertension. Previous history of...
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