Comparison of angiogenic and anti-angiogenic factors in maternal and umbilical cord blood in early- and late-onset pre-eclampsia

Objectives: Premature birth, defined as less than 37 weeks gestation, affects approximately 12% of all live births around the world. Advances in neonatal care have resulted in the increased survival of infants born prematurely. Although prematurity is a known risk factor for different cardiovascular diseases, little is known about the pathophysiology of vasculature during premature gestation and angiopoietic factors network during premature birth. Aims: The objective of this study was to determine whether the profile of several pro-angiogenic and anti-angiogenic factors in umbilical cord blood (UCB) is different in healthy appropriate-for-gestational-age preterm newborns and normal term babies. The second aim of this study was to investigate the microRNA (miRNAs) expression profile in UCB from preterm labor and to detect miRNAs potentially taking part in control of angogenesis-related processes (Angio-MiRs). Methods: Using an immunobead Luminex assay, we simultaneously measured the concentration of Angiogenin, Angiopoietin-1, FGF-acidic, FGF-basic, PDGF-aa, PlGF, VEGF, VEGF-D, Endostatin, Thrombospondin-2, NGF, BDNF, GDNF, and NT-4 in UCB samples collected from the preterm (n = 27) and term (n = 52) delivery. In addition, the global microRNA expression in peripheral blood mononuclear cells (PBMCs) circulating in such UCB samples was examined in this study using microarray MiRNA technique. Results: The concentrations of five from eight measured pro-angiogenic factors (VEGF, Angiopoietin-1, PDGF-AA, FGF-a, and FGF-b) were significantly lower in UCB from preterm newborns. On the contrary, two angiostatic factors (Endostatin and Thrombospondin-2) were significantly up-regulated in preterm UCB. Among analyzed neurotrophins in preterm newborns, the elevated UCB concentration was found only in the case of GDNF, whereas BDNF was significantly reduced. Moreover, two angiopoietic factors, VEGF-D and PlGF, and two neurotrophins, NT4 and NGF, did not differ in concentration in preterm and term babies. We also discovered that among the significantly down-regulated miRNAs, there were several classical Angio-MiRs (inter alia MiR-125, MiR-126, MiR-145, MiR-150, or MiR155), which are involved in angiogenesis regulation in newborn after preterm delivery. Conclusions: This is the first report of simultaneous measurements of several angiopoietic factors in UCB collected from infants during preterm and term labor. Here, we observed that several pro-angiogenic factors were at lower concentration in UCB collected from preterm newborns than term babies. In contrast, the two measured angiostatic factors, Endostatin and Thrombospondin-2, were significantly higher in UCB from preterm babies. This can suggest that distinct pathophysiological contributions from differentially expressed various angiopoietic factors may determine the clinical outcomes after preterm birth. Especially, our angiogenesis-related molecules analysis indicates that preterm birth of healthy, appropriate-for-gestational-age newborns is an “anti-angiogenic state” that may provide an increased risk for improper development and function of cardiovascular system in the adulthood. This work also contributes to a better understanding of the role of miRNAs potentially involved in angiogenesis control in preterm newborns.

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Differential expression of markers of oxidative stress and apoptosis in relation to serum ferritin levels in patients with pre-eclampsia

BioMedica ◽

10.51441/biomedica/5-512 ◽

2021 ◽

Vol 37 (3) ◽

pp. 1-8

Author(s):

Jianying Yan ◽

Jie Dong ◽

Xiaoqian Lin ◽

Lichun Chen ◽

Zhuanji Fang ◽

...

Keyword(s):

Oxidative Stress ◽

Cord Blood ◽

Umbilical Cord ◽

Serum Ferritin ◽

Umbilical Cord Blood ◽

Cell Apoptosis ◽

Late Onset ◽

Placental Tissue ◽

Control Group ◽

Pregnant Females

Background and Objective: Pre-eclampsia (PE) is a hypertensive gestational disease appearing during second trimester of pregnancy. Free radicals are released by the placenta in this condition that may cause oxidative damage. This study was designed to determine the serum ferritin (SF) levels in maternal blood, fetal umbilical cord blood and placenta and the changes associated with oxidative stress as well as cell apoptosis to understand the pathogenesis of PE. Methods: This cross-sectional analytical study recruited 60 pregnant females with severe PE and assigned into early and late onset PE groups. Another n = 60 cases of normal pregnant females with similar gestational weeks were selected in the control group. Maternal serum and fetal umbilical cord blood ferritin levels were determined by automatic biochemical immunoassay system. Reverse transcription real-time fluorescence, Western blot and colorimetry were used to determine mRNA expression levels of ferritin and ferritin heavy chain, relative expression of ferritin and superoxide dismutase, malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) levels, respectively. Results: Mean age was 30.89 ± 5.65 and 31.79 ± 5.06 years in early and late onset PE groups respectively. Serum uric acid and creatinine levels of both PE groups were significantly higher than the normal pregnant females. SF levels were also higher in the participants of PE groups. However, the mRNA and ferritin protein levels in placental tissue were significantly lower in PE groups while comparing to controls. The cleaved caspase-3 protein, GSH-Px and MDA levels were significantly higher in both PE groups (p < 0.05). Conclusion: The alterations in factors related to oxidative stress and cell apoptosis in placental tissue may be helpful to understand the pathogenesis of PE and may provide potential biomarkers for the diagnosis of PE.

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MiRNAs Regulating Oxidative Stress: A Correlation with Doppler Sonography of Uteroplacental Complex and Clinical State Assessments of Newborns in Fetal Growth Restriction

Journal of Clinical Medicine ◽

10.3390/jcm9103227 ◽

2020 ◽

Vol 9 (10) ◽

pp. 3227

Author(s):

Vladislava Gusar ◽

Mariya Ganichkina ◽

Vitaliy Chagovets ◽

Nataliya Kan ◽

Gennadiy Sukhikh

Keyword(s):

Oxidative Stress ◽

Cord Blood ◽

Umbilical Cord ◽

Fetal Growth ◽

Umbilical Cord Blood ◽

Fetal Growth Restriction ◽

Early Onset ◽

Umbilical Artery ◽

Late Onset ◽

Perinatal Outcomes

Overproduction of reactive oxygen species (ROS) and, as a result, uncontrolled oxidative stress (OS) can play a central role in disorders of fetal hemodynamics and subsequent development of adverse perinatal outcomes in newborns with fetal growth restriction (FGR). Given the epigenetic nature of such disorders, the aim of our study was to evaluate the expression of miRNAs associated with OS and endothelial dysfunction (miR-27a-3p, miR-30b-5p, miR-125b-5p, miR-221-3p, miR-451a and miR-574-3p) in umbilical cord blood using real-time quantitative RT-PCR. ΜiRNA expression was evaluated in patients with FGR delivery before (n = 9 pregnant) and after 34 weeks of gestation (n = 13 pregnant), and the control groups corresponding to the main groups by gestational age (13 pregnant women in each group, respectively). A significant increase in miR-451a expression was detected in late-onset FGR and correlations with fetoplacental and cerebral circulation were established (increase of resistance in the umbilical artery (pulsatility index, PI UA (umbilical artery): r = −0.59, p = 0.001) and a decrease in cerebral blood flow (CPR: r = 0.48, p = 0.009)). The change in miR-125b-5p expression in the placenta is associated with reduced Doppler of cerebral hemodynamics (CPR: r = 0.73, p = 0.003; PI MCA (middle cerebral artery): r = 0.79, p = 0.0007), and newborn weight (r = 0.56, p = 0.04) in early-onset FGR. In addition, significant changes in miR-125b-5p and miR-451a expression in umbilical cord blood plasma were found in newborns with neonatal respiratory distress syndrome (NRDS) (in early-onset FGR) and very low birth weight (VLBW) (in late-onset FGR). A number of key signaling pathways have been identified in which the regulation of the studied miRNAs is involved, including angiogenesis, neurotrophin signaling pathway and oxidative stress response. In general, our study showed that changes of the redox homeostasis in the mother-placenta-fetus system in FGR and subsequent perinatal outcomes may be due to differential expression of oxidative stress-associated miRNAs.

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Iron metabolism disorder and oxidative damage levels in placenta are involved in preeclampsia

Archives of Medical Science ◽

10.5114/aoms/144629 ◽

2021 ◽

Author(s):

Jianying Yan ◽

Jie Dong ◽

Xiaoqian Lin ◽

Lichun Chen ◽

Zhuanji Fang ◽

...

Keyword(s):

Cord Blood ◽

Pregnant Women ◽

Blood Sample ◽

Umbilical Cord ◽

Umbilical Cord Blood ◽

Early Onset ◽

Late Onset ◽

Control Group ◽

Cord Blood Sample ◽

Stress Injury

IntroductionTo explore the role of ferritin in placenta, serum and umbilical cord blood of pregnant women and the changes of oxidative stress injury as well as cell apoptosis in placenta in the pathogenesis of preeclampsia (PE).Material and methodsSixty pregnant women with severe PE were assigned into early-onset and late-onset PE group. Another 60 cases of normal late pregnant women with similar gestational weeks were divided into early-onset and late-onset control group. Maternal serum and fetal umbilical cord blood ferritin content was determined by automatic biochemical immunoassay system; mRNA expression levels of ferritin and ferritin heavy chain (FTH) were detected by reverse transcription real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). Western Blot was used to detect the relative expression level of ferritin and apoptosis; the contents of total superoxide dismutase (T-SOD) and malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) were detected by colorimetry.ResultsSerum uric acid (UA) and creatinine (Cr) levels of PE groups were significantly higher when compared to the controls. The serum ferritin levels in blood sample and umbilical cord blood sample were significantly higher relative to the controls. However, the mRNA and protein levels of ferritin levels in placenta samples were significantly lower compared with the controls. The placental cleaved caspase-3, Bcl-2 levels were significantly lower than the early onset PE group. The levels of GSH-Px and MDA in placenta were significantly higher.ConclusionsThese results may assist understanding the pathogenesis of PE and provide potential biomarkers for diagnosis of PE.

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