Ilona Hromadnikova1, Katerina Kotlabova2, Katarina Ivankova3, Yulia Vedmetskaya3, Ladislav Krofta3. 1. Department of Molecular Biology and Cell Pathology, Third Faculty of Medicine, Charles University, Prague, Czech Republic. Electronic address: Ilona.Hromadnikova@lf3.cuni.cz. 2. Department of Molecular Biology and Cell Pathology, Third Faculty of Medicine, Charles University, Prague, Czech Republic. 3. Institute for the Care of the Mother and Child, Third Faculty of Medicine, Charles University, Prague, Czech Republic.
Abstract
BACKGROUND AND METHODS: Gene expression of 29 cardiovascular and cerebrovascular disease associated microRNAs was assessed in whole umbilical cord blood, compared between groups [47 gestational hypertension (GH), 56 preeclampsia (PE), 37 fetal growth restriction (FGR) and 44 normal pregnancies] and correlated with the severity of the disease with respect to clinical signs (mild PE vs. severe PE), delivery date (before and after 34weeks of gestation), and Doppler ultrasound parameters [pulsatility index (PI) in the umbilical artery, PI in the middle cerebral artery and the cerebroplacental ratio]. RESULTS: GH showed a down-regulation of miR-195-5p (p=0.025). The down-regulation of miR-26a-5p (p=0.031, p=0.05), miR-145-5p (p=0.042, p=0.015), and miR-574-3p (p=0.002, p=0.022) was observed in severe PE pregnancies requiring termination before 34weeks of gestation. Severe PE occurring regardless of the delivery date was associated with downregulation of miR-195-5p (p=0.01), miR-199a-5p (p=0.048), and miR-221-3p (p=0.028). On the other hand, mild PE showed upregulation of miR-92a-3p (p=0.044). The centralization of fetal circulation tended to higher levels of miR-1-3p (ρ=-0.302, p=0.045) and miR-133a-3p (ρ=-0.348, p=0.020) in PE pregnancies. FGR pregnancies with abnormal values of flow rate in the umbilical artery (miR-221-3p: ρ=-0.390, p=0.017) and the middle cerebral artery (miR-143-3p: ρ=0.350, p=0.036) demonstrated down-regulation of relevant microRNAs. CONCLUSION: Epigenetic changes induced by pregnancy-related complications in umbilical cord blood may appear as a result of dysfunctional placenta and impaired maternal cardiovascular function (hidden cardiovascular and cerebrovascular diseases) and may cause later onset of cardiovascular and cerebrovascular diseases in offspring.
BACKGROUND AND METHODS: Gene expression of 29 cardiovascular and cerebrovascular disease associated microRNAs was assessed in whole umbilical cord blood, compared between groups [47 gestational hypertension (GH), 56 preeclampsia (PE), 37 fetal growth restriction (FGR) and 44 normal pregnancies] and correlated with the severity of the disease with respect to clinical signs (mild PE vs. severe PE), delivery date (before and after 34weeks of gestation), and Doppler ultrasound parameters [pulsatility index (PI) in the umbilical artery, PI in the middle cerebral artery and the cerebroplacental ratio]. RESULTS: GH showed a down-regulation of miR-195-5p (p=0.025). The down-regulation of miR-26a-5p (p=0.031, p=0.05), miR-145-5p (p=0.042, p=0.015), and miR-574-3p (p=0.002, p=0.022) was observed in severe PE pregnancies requiring termination before 34weeks of gestation. Severe PE occurring regardless of the delivery date was associated with downregulation of miR-195-5p (p=0.01), miR-199a-5p (p=0.048), and miR-221-3p (p=0.028). On the other hand, mild PE showed upregulation of miR-92a-3p (p=0.044). The centralization of fetal circulation tended to higher levels of miR-1-3p (ρ=-0.302, p=0.045) and miR-133a-3p (ρ=-0.348, p=0.020) in PE pregnancies. FGR pregnancies with abnormal values of flow rate in the umbilical artery (miR-221-3p: ρ=-0.390, p=0.017) and the middle cerebral artery (miR-143-3p: ρ=0.350, p=0.036) demonstrated down-regulation of relevant microRNAs. CONCLUSION: Epigenetic changes induced by pregnancy-related complications in umbilical cord blood may appear as a result of dysfunctional placenta and impaired maternal cardiovascular function (hidden cardiovascular and cerebrovascular diseases) and may cause later onset of cardiovascular and cerebrovascular diseases in offspring.