Fetal Oxidative Stress Research Articles

Protect-me: a parallel-group, triple blinded, placebo-controlled randomised clinical trial protocol assessing antenatal maternal melatonin supplementation for fetal neuroprotection in early-onset fetal growth restriction

IntroductionFetal growth restriction (FGR) is a serious pregnancy complication, associated with increased rates of perinatal death and morbidity among survivors. Most commonly FGR results from placental insufficiency, where the placenta...

Intervention against hypertension in the next generation programmed by developmental hypoxia.

Evidence derived from human clinical studies and experimental animal models shows a causal relationship between adverse pregnancy and increased cardiovascular disease in the adult offspring. However, translational studies isolating mechanisms to design intervention are lacking. Sheep and humans share similar precocial developmental milestones in cardiovascular anatomy and physiology. We tested the hypothesis in sheep that maternal treatment with antioxidants protects against fetal growth restriction and programmed hypertension in adulthood in gestation complicated by chronic fetal hypoxia, the most common adverse consequence in human pregnancy. Using bespoke isobaric chambers, chronically catheterized sheep carrying singletons underwent normoxia or hypoxia (10% oxygen [O2]) ± vitamin C treatment (maternal 200 mg.kg−1 IV daily) for the last third of gestation. In one cohort, the maternal arterial blood gas status, the value at which 50% of the maternal hemoglobin is saturated with oxygen (P50), nitric oxide (NO) bioavailability, oxidative stress, and antioxidant capacity were determined. In another, naturally delivered offspring were raised under normoxia until early adulthood (9 months). Lambs were chronically instrumented and cardiovascular function tested in vivo. Following euthanasia, femoral arterial segments were isolated and endothelial function determined by wire myography. Hypoxic pregnancy induced fetal growth restriction and fetal oxidative stress. At adulthood, it programmed hypertension by enhancing vasoconstrictor reactivity and impairing NO-independent endothelial function. Maternal vitamin C in hypoxic pregnancy improved transplacental oxygenation and enhanced fetal antioxidant capacity while increasing NO bioavailability, offsetting constrictor hyper-reactivity and replenishing endothelial function in the adult offspring. These discoveries provide novel insight into mechanisms and interventions against fetal growth restriction and adult-onset programmed hypertension in an animal model of complicated pregnancy in a species of similar temporal developmental milestones to humans.

Effects of prenatal oxidative stress levels on fetal programming: Results from the NELA birth cohort

Introduction The Developmental Origins of Health and Diseases (DOHaD) hypothesis states that both the pre- and postnatal environments shape health and disease later in life. Prenatal oxidative stress can have long term health consequences in the offspring through developmental programming, including an increased risk of adiposity; however studies in humans are limited. We aim to investigate the effects of prenatal oxidative stress levels on birth size measures used as proxies of fetal adiposity development. Methods Data come from the Nutrition and Early Life Asthma (NELA) study, a population-based birth cohort set up in 2015 in Spain. Maternal fasting blood samples were drawn at 24 weeks of gestation and newborn cord blood samples were collected at birth to analyze for oxidative stress markers, including protein carbonyl (protein oxidation), hydroperoxides (lipid oxidation), and 8-hydroxy-2’ -deoxyguanosine (DNA oxidation). Maternal and newborn antioxidant status was assessed by glutathione peroxidase, catalase, the trolox equivalent antioxidant capacity (TEAC), and the ferric reducing ability of plasma (FRAP). In addition, vitamin A and E levels were assessed as a measured of exogenous antioxidant markers. In multivariable regression models we assessed the association between maternal and newborn biomarkers with birth size measures including weight and length-derived anthropometric indicators: weight-for-age z score, weight-for-length z score, and BMI-for age z score as proxies of body composition; skinfold thickness as a proxy for subcutaneous adiposity; and length z score, which is considered as a proxy for lean mass. Results Maternal and newborn FRAP, TEAC and protein carbonyl levels were positively correlated (correlation coefficients range 0.45–0.63, P-values Conclusions Fetal antioxidant capacity and exogenous antioxidant levels (i.e. vitamin A) may influence body composition at birth. These results could help to unravel the link between prenatal oxidative stress with fetal programming and long term health consequences for the offspring. In addition, the results will shed new light on prenatal factors that may perturb maternal and fetal oxidative stress status providing new insights of the biological pathways central to fetal programming.

Beneficial Effects of Curcumin in Maternal and Fetal Oxidative Stress and Brain Damage Induced by Gestational Lead Administration

This study was planned to explore the protective role of curcumin (Cur) against maternal and fetal oxidative stress and cerebral damage induced by lead (Pb) during pregnancy. Positively pregnant female rats were divided into seven groups: control group, Cur group (300 mg/kg of Cur/b.wt.), DMSO group (50% DMSO), two Pb-treated groups (exposed to 160 and 320 mg/kg b.wt./day of Pb acetate, respectively), and two groups treated with both Pb and Cur (exposed to Pb as previous groups together with 300 mg/kg b.wt./day of Cur). Treatments through oral gavage once a day started from gestation day 1 (GD1) till day 20 (GD20), where the mother rats of different experimental groups were sacrificed to obtain the fetuses. Different chemical parameters were assessed. Brain specimens of mother and fetal groups were processed with examination. The results displayed that Pb administration to pregnant rats resulted in a dose-dependent toxicity for both mothers and fetuses. Also, there was a significant rise in lipid peroxidation and decreased antioxidant enzyme activities in the brains of the different Pb-treated groups. The histological examination of the brain of treated dams and fetuses showed marked alterations. Co-treatment of Cur along with Pb caused a significant decrease in Pb levels as compared with those treated with Pb alone, improving the oxidative condition with amelioration of the brain’s histopathological changes. Co-administration of Cur could have ameliorative effect against Pb-induced neurotoxicity through the reduction of oxidative stress and reversal of histopathological changes.

Effect of maternal oxygen inhalation on foetal free radical activity: a prospective, randomized trial.

Maternal inhalation of 35-40% oxygen concentration has no significant effect on foetal partial pressure of oxygen, and 60-100% produced maternal and foetal hyperoxia with increased free radical activity. The benefit of 50% maternal oxygen inhalation on foetal oxygenation, oxidant stress and total antioxidant status (TAS) during Caesarean section (CS) has not been simultaneously evaluated. In this prospective, randomized, controlled trial 120 ASA physical status I-II, term pregnant women were recruited to elective CS (n = 60) and emergency CS (n = 60) and received either 50% oxygen or air inhalation following subarachnoid block (SAB). Patients and investigators were blinded to the inhaled oxygen concentration. The primary outcome of the study was foetal umbilical artery (UA) malondialdehyde (MDA) at birth. In both elective and emergency CS, there was no difference in foetal oxidative stress and TAS in spite of increase in maternal PaO2. In elective CS, maternal MDA was higher at delivery in mothers breathing 50% oxygen as compared to their own baseline values (P = 0.04). In emergency CS, maternal TAS at 10 min was lower in mothers inhaling 50% oxygen as compared to air (P = 0.01). The average duration of maternal oxygen supplementation was ~10.3 min in elective and ~7.4 min in emergency CS. Neonatal outcome, episodes of maternal hypotension and oxygen desaturation were similar in both the groups. Brief duration of 50% oxygen maternal inhalation during elective or emergency CS did not significantly affect foetal MDA and TAS under SAB.

Fructose during pregnancy provokes fetal oxidative stress: The key role of the placental heme oxygenase-1.

One of the features of metabolic syndrome caused by liquid fructose intake is an impairment of redox status. We have investigated whether maternal fructose ingestion modifies the redox status in pregnant rats and their fetuses. Fructose (10% wt/vol) in the drinking water of rats throughout gestation, leads to maternal hepatic oxidative stress. However, this change was also observed in glucose-fed rats and, in fact, both carbohydrates produced a decrease in antioxidant enzyme activity. Surprisingly, mothers fed carbohydrates displayed low plasma lipid oxidation. In contrast, fetuses from fructose-fed mothers showed elevated levels of plasma lipoperoxides versus fetuses from control or glucose-fed mothers. Interestingly, a clearly augmented oxidative stress was observed in placenta of fructose-fed mothers, accompanied by a lower expression of the transcription factor Nuclear factor-erythroid 2-related factor-2 (Nrf2) and its target gene, heme oxygenase-1 (HO-1), a potent antioxidant molecule. Moreover, histone deacetylase 3 (HDAC3) that has been proposed to upregulate HO-1 expression by stabilizing Nrf2, exhibited a diminished expression in placenta of fructose-supplemented mothers. Maternal fructose intake provoked an imbalanced redox status in placenta and a clear diminution of HO-1 expression, which could be responsible for the augmented oxidative stress found in their fetuses.

Abstract 031: Placental Ischemia Causes Mitochondrial Dysfunction in Reduced Uterine Perfusion Pressure Rats

Introduction: Placental ischemia is believed to be the initial event in the development of preeclampsia (PE). PE is characterized by new onset hypertension and is associated with reduced fetal weight and placental oxidative stress. Mitochondrial dysfunction is the major cause of reactive oxygen species (ROS) generation. We hypothesize that the placental ischemia causes mitochondrial dysfunction in the reduced uterine perfusion pressure (RUPP) rat model of PE. Thus, the purpose of this study is to examine the effect of placental ischemia on mitochondrial function. Methods: Female Sprague Dawley rats were dived into two groups; normal pregnant (NP) and RUPP rats. On gestational day (GD) 14, RUPP surgery was performed, GD18 carotid catheters were inserted, and GD19 conscious blood pressure (MAP) was measured. GD 19 placentas were collected and mitochondria were isolated for respiration measurements. Respiration measurements included: basal state (isolated mitochondria with no substrates), state 2 (glutamate and malate as complex I substrates), state 3 (ADP stimulated), leak state (oligomycin induced ATP synthase inhibition), and maximal state (FCCP stimulated uncoupled). Cytochrome C oxidase (complex IV) activity was also measured in isolated mitochondria. Results: MAP was elevated in RUPP (n=16) compared to NP rats (n=14) (119±2 vs. 100±2 mmHg, p<0.05). State 3 (149±8 vs 220±12 pmol/sec/mg, p<0.05) and maximal (123±8 vs 159±5 pmol/sec/mg, p<0.05) respiration rates were significantly reduced in RUPP (n=5) vs NP (n=7) rats. However, basal, state 2, and state 4 respiratory rates were not different between RUPP vs NP. Respiratory control ratio (state 3/ state 4) was significantly reduced in RUPP (n=5) vs NP (n=7) (7±1 vs 10±1, p<0.05). Complex IV activity was reduced in RUPP (n=5) vs. NP (n=6) rats (508±14 vs 644±17 nmol e-/min/mg, P<0.05). Conclusion: Reduced mitochondrial respiration and cytochrome c oxidase activity, indicators of mitochondrial dysfunction, occur in response to placental ischemia during pregnancy. Thus, suggesting that mitochondrial dysfunction may contribute to the pathophysiology of oxidative stress and hypertension during PE.

Fetal alcohol syndrome-induced oxidative stress and antioxidant mechanism

Alkol bircok organ ve dokuda (ozellikle beyin ve karaciger) doza ve kullanim suresine bagli olarak hasar olusturabilen bir toksindir. Dogum oncesi(prenatal) donemde anne tarafindan kullanilan alkol, fetal alkol sendromuna neden olabilmektedir. Fetal alkol sendromu ilk olarak 1970’li yillarinbasinda, alkol kullanma aliskanligini gebelikte de surduren anneden dogan bebeklerde gorulen buyume bozuklugu, yuz bolgesi anormallikleri vemental gerilik olarak tanimlanmistir. Gebeligin ilk uc ayinda kullanilan alkol fetus uzerinde dusuge, organogenez doneminde organlarda hasara,gebeligin ikinci uc aylik doneminde hucrelerdeki fetotoksik etkisiyle merkezi sinir sisteminde agir hasara neden olabilmektedir. Bu derlemede dogumoncesi alkol kullanimi sonucu olusan oksidatif stres ve antioksidan savunma mekanizmasi hakkinda bilgiler sunulmustur.

Fetal oxidative stress mechanisms of neurodevelopmental deficits and exacerbation by ethanol and methamphetamine.

In utero exposure of mouse progeny to alcohol (ethanol, EtOH) and methamphetamine (METH) causes substantial postnatal neurodevelopmental deficits. One emerging pathogenic mechanism underlying these deficits involves fetal brain production of reactive oxygen species (ROS) that alter signal transduction, and/or oxidatively damage cellular macromolecules like lipids, proteins, and DNA, the latter leading to altered gene expression, likely via non-mutagenic mechanisms. Even physiological levels of fetal ROS production can be pathogenic in biochemically predisposed progeny, and ROS formation can be enhanced by drugs like EtOH and METH, via activation/induction of ROS-producing NADPH oxidases (NOX), drug bioactivation to free radical intermediates by prostaglandin H synthases (PHS), and other mechanisms. Antioxidative enzymes, like catalase in the fetal brain, while low, provide critical protection. Oxidatively damaged DNA is normally rapidly repaired, and fetal deficiencies in several DNA repair proteins, including oxoguanine glycosylase 1 (OGG1) and breast cancer protein 1 (BRCA1), enhance the risk of drug-initiated postnatal neurodevelopmental deficits, and in some cases deficits in untreated progeny, the latter of which may be relevant to conditions like autism spectrum disorders (ASD). Risk is further regulated by fetal nuclear factor erythroid 2-related factor 2 (Nrf2), a ROS-sensing protein that upregulates an array of proteins, including antioxidative enzymes and DNA repair proteins. Imbalances between conceptal pathways for ROS formation, versus those for ROS detoxification and DNA repair, are important determinants of risk. Birth Defects Research (Part C) 108:108-130, 2016. © 2016 Wiley Periodicals, Inc.

206: Sex-specific effects of maternal obesity on embryo size and fetal brain oxidative stress

206: Sex-specific effects of maternal obesity on embryo size and fetal brain oxidative stress

Maternal melatonin administration mitigates coronary stiffness and endothelial dysfunction, and improves heart resilience to insult in growth restricted lambs

Intrauterine growth restriction (IUGR) is associated with impaired cardiac function in childhood and is linked to short- and long-term morbidities. Placental dysfunction underlies most IUGR, and causes fetal oxidative stress which may impact on cardiac development. Accordingly, we investigated whether antenatal melatonin treatment, which possesses antioxidant properties, may afford cardiovascular protection in these vulnerable fetuses. IUGR was induced in sheep fetuses using single umbilical artery ligation on day 105-110 of pregnancy (term 147). Study 1: melatonin (2 mg h(-1)) was administered i.v. to ewes on days 5 and 6 after surgery. On day 7 fetal heart function was assessed using a Langendorff apparatus. Study 2: a lower dose of melatonin (0.25 mg h(-1)) was administered continuously following IUGR induction and the ewes gave birth normally at term. Lambs were killed when 24 h old and coronary vessels studied. Melatonin significantly improved fetal oxygenation in vivo. Contractile function in the right ventricle and coronary flow were enhanced by melatonin. Ischaemia-reperfusion-induced infarct area was 3-fold greater in IUGR hearts than in controls and this increase was prevented by melatonin. In isolated neonatal coronary arteries, endothelium-dependent nitric oxide (NO) bioavailability was reduced in IUGR, and was rescued by modest melatonin treatment. Melatonin exposure also induced the emergence of an indomethacin-sensitive vasodilation. IUGR caused marked stiffening of the coronary artery and this was prevented by melatonin. Maternal melatonin treatment reduces fetal hypoxaemia, improves heart function and coronary blood flow and rescues cardio-coronary deficit induced by IUGR.

Placental oxidative stress and decreased global DNA methylation are corrected by copper in the Cohen diabetic rat

Fetal Growth Restriction (FGR) is a leading cause for long term morbidity. The Cohen diabetic sensitive rats (CDs), originating from Wistar, develop overt diabetes when fed high sucrose low copper diet (HSD) while the original outbred Sabra strain do not. HSD induced FGR and fetal oxidative stress, more prominent in the CDs, that was alleviated more effectively by copper than by the anti-oxidant vitamins C and E. Our aim was to evaluate the impact of copper or the anti-oxidant Tempol on placental size, protein content, oxidative stress, apoptosis and total DNA methylation. Animals were mated following one month of HSD or regular chow diet and supplemented throughout pregnancy with either 0, 1 or 2ppm of copper sulfate or Tempol in their drinking water. Placental weight on the 21st day of pregnancy decreased in dams fed HSD and improved upon copper supplementation. Placental/fetal weight ratio increased among the CDs. Protein content decreased in Sabra but increased in CDs fed HSD. Oxidative stress biochemical markers improved upon copper supplementation; immunohistochemistry for oxidative stress markers was similar between strains and diets. Caspase 3 was positive in more placentae of dams fed HSD than those fed RD. Placental global DNA methylation was decreased only among the CDs dams fed HSD. We conclude that FGR in this model is associated with smaller placentae, reduced DNA placental methylation, and increased oxidative stress that normalized with copper supplementation. DNA hypomethylation makes our model a unique method for investigating genes associated with growth, oxidative stress, hypoxia and copper.

New evaluation of fetal oxidative stress: measurement of the umbilical cord blood dimethyl sulfate-induced ascorbyl-free radical by an electron spin resonance method

Objective: The aim is to evaluate intrapartum fetal oxidative stress in real-time by umbilical cord blood dimethyl sulfate (DMSO)-induced ascorbyl-free radical (AFR) measured by an electron spin resonance (ESR) method.Methods: Seventy-five mothers delivering at gestational age after 37 weeks were recruited. They were divided into three groups: spontaneous vaginal birth (n = 27), elective cesarean section (CS) (n = 34), and emergency CS due to non-reassuring fetal status (n = 14). Umbilical artery (UA) and venous (UV) cord blood gas analysis was performed. Serum levels of DMSO-induced AFR (AFR/DMSO) that reflect vitamin C concentrations were measured by ESR spectroscopy.Results: Blood gas analysis showed no significant differences among the groups. UA-AFR/DMSO level of elective CS group was significantly lower compared with spontaneous delivery group (0.32 ± 0.12 versus 0.46 ± 0.14, p < 0.005). Emergency CS group showed significantly lower levels of UA-AFR/DMSO compared with elective CS group (0.25 ± 0.11 versus 0.32 ± 0.12, p < 0.005). UV-AFR/DMSO levels had no significant difference among the groups.Conclusions: It is suggested that fetal cord blood AFR/DMSO is a sensitive marker to assess fetal oxidative stress during delivery.

Supplemental Oxygen in Elective Cesarean Section under Spinal Anesthesia: Handle the Sword with Care

Background and objectives: We aimed to investigate the effect of 21% and 40% oxygen supplementation on maternal and neonatal oxidative stress in elective cesarean section (CS) under spinal anesthesia. MethodsEighty term parturients undergoing elective CS under spinal anesthesia were enrolled in the study. We allocated patients randomly to breathe 21% (air group) or 40% (oxygen group) oxygen from the time of skin incision until the end of the operation. We collected maternal pre- and post-operative and umbilical artery (UA) blood samples. Total antioxidant capacity (TAC), total oxidant status (TOS) and the oxidative stress index (OSI) were measured. ResultsAge, weight, height, parity, gestation week, spinal-skin incision time, skin incision-delivery time, delivery time, operation time, 1st and 5th minutes Apgar scores, and birth weight were similar between the groups (p > 0.05 for all comparisons). There were no differences in preoperative TAC, TOS, or OSI levels between the groups (p > 0.05 for all comparisons). Postoperative maternal TAC, TOS and OSI levels significantly increased in the oxygen group (p = 0.047, < 0.001 and 0.038, respectively); umbilical artery TAC levels significantly increased in the oxygen group (p = 0.003); and umbilical artery TOS and OSI levels significantly increased in the air group (p = 0.02 and < 0.001, respectively). ConclusionsThe difference in impact on maternal and fetal oxidative stress of supplemental 40% compared to 21% oxygen mandates further large-scale studies that investigate the role of oxygen supplementation during elective CS under spinal anesthesia.

Differences in levels of oxidative stress in mothers and neonate: the impact of mode of delivery

Objective: To determine there are differences in the production levels of oxygen free radical between mothers and neonates by the mode of delivery, we measured oxygen free radical concentrations in maternal vein and umbilical artery.Methods: Forty-four women with singleton term pregnancies were prospectively recruited and classified into two groups: those who had a spontaneous uncomplicated vaginal delivery (VD group; n = 21), and those who had an elective cesarean delivery (CD group; n = 23). We determined maternal and fetal oxidative stress levels by measuring concentrations of derivatives of reactive oxygen metabolites (d-ROMs) in maternal vein before delivery and on postnatal day 5, and in umbilical artery at delivery. We also measured the pH, partial pressure of oxygen (PaO2), partial pressure of carbon dioxide (PaCO2) and base excess (BE) in umbilical artery blood collected at delivery.Results: The concentrations of d-ROMs in maternal vein on postnatal day 5 were significantly decreased in the VD group, but were significantly increased in the CD group, compared to before delivery. The concentrations of d-ROMs in umbilical artery were significantly higher in the VD group than the CD group. Compared to the CD group, umbilical artery pH tended to be lower (p = 0.07), and BE significantly lower (p < 0.005), in the VD group. There were no significant differences in umbilical artery PaO2 and PaCO2 between the two groups.Conclusion: Our findings indicate that those production levels of oxygen free radical in mothers are greater by CD than by VD, while those in neonates are greater by VD than by CD.

Dietary supplementation with Ipomoea aquatica (whole leaf powder) attenuates maternal and fetal oxidative stress in streptozotocin‐diabetic rats (饮食中添加蕹菜（整叶粉末）可以减弱链脲霉素诱导的糖尿病大鼠母体与胚胎的氧化应激)

AbstractBackground: The rate of congenital anomalies, as well as morbidity and mortality of both the mother and fetus, is increased in diabetic pregnancy. Oxidative stress (OS) has been implicated in these effects because of the beneficial effects of several antioxidants in diabetic embryopathy. In the present study, we assessed attenuation of maternal and fetal OS and diabetic embryopathy by Ipomoea aquatica Forsk. (Convolvulaceae).Methods: Pregnant rats were divided into four groups: Group I, untreated non‐diabetic control; Group II, rats fed a 2%I. aquatica (IA)‐supplemented diet; Group III, streptozotocin (STZ)‐diabetic rats fed a normal diet; Group IV, STZ‐diabetic rats fed an IA‐supplemented diet. Rats were rendered diabetic with a single injection of STZ (40 mg/kg) on gestational day (GD) 4. Dams were killed on GD20 and markers of OS were determined in the maternal liver and fetal brain and liver.Results: Embryopathy increased significantly in STZ‐diabetic rats (by 40% versus control), but IA supplementation provided significant protection (36% reduction in embryopathy in the IA group versus the STZ‐diabetic group). Interestingly, IA supplementation significantly offset diabetes‐associated OS in the maternal liver, as evidenced by reductions in malondialdehyde (MDA; 25% reduction versus STZ‐diabetes) and reactive oxygen species (ROS; 72% reduction) and increases in glutathione (53% reduction) and total thiols (45% reduction). In addition, IA supplementation offered significant protection against diabetes‐induced OS in the fetal brain and liver, as evidenced by increased levels of antioxidant molecules and enzymes and reductions in ROS and MDA compared with fetuses from STZ‐diabetic rats.Conclusions: The data suggest that IA supplementation during pregnancy provides considerable protection against diabetes‐induced OS in the mother and fetus. Thus, I. aquatica may be an effective therapeutic supplement.

Amniotic Fluid Oxidative and Nitrosative Stress Biomarkers Correlate with Fetal Chronic Hypoxia in Diabetic Pregnancies

Background: In spite of improvement in obstetrical care, pregnancy in women with type 1 diabetes mellitus is associated with increased perinatal morbidity and mortality. Hyperglycemia during pregnancy causes excessive fetal growth and chronic fetal hypoxia as reflected in increased erythropoietin (EPO) levels in amniotic fluid (AF). Objectives: We hypothesized that the degree of fetal hypoxia would correlate with fetal oxidative and nitrosative stress as evidenced by the concentration of specific biomarkers in AF. Material and Methods: 19 pregnant women with type 1 or insulin-treated gestational diabetes mellitus were studied. AF samples were collected and processed for EPO, meta-tyrosine, nitro-tyrosine and 8-hydroxy-2-deoxiguanosine by chemiluminescent immunoassay and high-performance liquid chromatography coupled to tandem mass spectrometry methods, respectively. Results: The mean (SD) of the last HbA_1c concentration before delivery was 7.7% (1.1). Median gestational age was 258 days (range 231–268). Birth weight was 3,868 ± 695 g with a z-score >2 SD in 47% of the cases. A significant correlation was found between the concentrations of AF EPO and meta-tyrosine/phenylalanine ratio (p < 0.001), nitro-tyrosine (p < 0.01) and 8-oxo-dG/2dG ratio (p < 0.001). Conclusions: We confirmed that fetuses of type 1 diabetes or insulin-treated gestational diabetes pregnancies experience chronic hypoxia as reflected by increased EPO concentrations in AF near term. Moreover, EPO levels significantly correlated with the concentration of oxidative and nitrosative stress biomarkers in AF. This pro-oxidant status may predispose newborn infants to poor postnatal adaptation and early neonatal complications.

New evaluation of fetal oxidative stress: measurement of the umbilical cord blood dimethyl sulfate-induced ascorbyl free radical by an electron spin resonance method

Objective: The aim is to evaluate intrapartum fetal oxidative stress in real-time by umbilical cord blood dimethyl sulfate (DMSO)-induced ascorbyl free radical (AFR) measured by an electron spin resonance (ESR) method. Methods: 75 mothers delivering at gestational age after 37 weeks were recruited. They were divided into three groups: spontaneous vaginal birth (n = 27), elective cesarean section (CS) (n = 34), and emergency CS due to non-reassuring fetal status (n = 14). Umbilical artery (UA) and venous (UV) cord blood gas analysis was performed. Serum levels of DMSO-induced AFR (AFR/DMSO) that reflect vitamin C concentrations, was measured by ESR spectroscopy. Results: Blood gas analysis showed no significant differences among the groups. UA-AFR/DMSO level of elective CS group was significantly lower compared with spontaneous delivery group (0.32 ± 0.12 vs. 0.46 ± 0.14, p < 0.005). Emergency CS group showed significantly lower levels of UA-AFR/DMSO compared with elective CS group (0.25 ± 0.11 vs. 0.32 ± 0.12, p < 0.005). UV-AFR/DMSO levels had no significant difference among the groups. Conclusions: It is suggested that fetal cord blood AFR/DMSO is a sensitive marker to assess fetal oxidative stress during delivery.

Cell Free Expression of hif1α and p21 in Maternal Peripheral Blood as a Marker for Preeclampsia and Fetal Growth Restriction

Preeclampsia, a severe unpredictable complication of pregnancy, occurs in 6% of pregnancies, usually in the second or third trimester. The specific etiology of preeclampsia remains unclear, although the pathophysiological hallmark of this condition appears to be an inadequate blood supply to the placenta. As a result of the impaired placental blood flow, intrauterine growth restriction (IUGR) and consequential fetal oxidative stress may occur. Consistent with this view, pregnancies complicated by preeclampsia and IUGR are characterized by up-regulation of key transcriptional regulators of the hypoxic response including, hif1α and as well as p53 and its target genes. Recently, the presence of circulating cell-free fetal RNA has been documented in maternal plasma. We speculated that pregnancies complicated by preeclampsia and IUGR, will be associated with an abnormal expression of p53 and/or hif1α related genes in the maternal plasma. Maternal plasma from 113 singleton pregnancies (72 normal and 41 complicated pregnancies) and 19 twins (9 normal and 10 complicated pregnancies) were collected and cell free RNA was extracted. The expression of 18 genes was measured by one step real-time RT-PCR and was analyzed for prevalence of positive/negative expression levels. Results indicate that, among the genes examined, cell free plasma expressions of p21 and hif1α were more prevalent in pregnancies complicated by hypoxia and/or IUGR (p<0.001). To conclude, we present in this manuscript data to support the association between two possible surrogate markers of hypoxia and common complications of pregnancy. More work is needed in order to implement these findings in clinical practice.

Fetal oxidative stress, DNA damage and repair in methamphetamine neurodevelopmental deficits in mice

Fetal oxidative stress, DNA damage and repair in methamphetamine neurodevelopmental deficits in mice