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11 pages, 422 KiB

Open AccessArticle

Low Levels of Vitamin C during Pregnancy; a Risk Marker of Progression of Diabetic Retinopathy in Type 1 Diabetic Women?

by Bente Juhl, Flemming Klein, Toke Bek and Line Petersen

Antioxidants 2023, 12(3), 576; https://doi.org/10.3390/antiox12030576 - 25 Feb 2023

Viewed by 1446

Abstract

Pregnancy is a risk factor for the development or aggravation of diabetic retinopathy. Here, we suggest a relationship between plasma vitamin C (vitC) status during pregnancy and into postpartum in type 1 diabetes and the possible progression of diabetic retinopathy based on data [...] Read more.

Pregnancy is a risk factor for the development or aggravation of diabetic retinopathy. Here, we suggest a relationship between plasma vitamin C (vitC) status during pregnancy and into postpartum in type 1 diabetes and the possible progression of diabetic retinopathy based on data of 29 women. VitC was measured in first, second, and third trimesters and three months postpartum. The women had visual acuity testing and fundus photography performed at least twice during pregnancy and onto four months after birth. An overall retinopathy grade was assigned on a scale from 0 (no retinopathy) to four according to the International Clinical Diabetic Retinopathy scale. At baseline in 1st trimester, 12 women had no retinopathy; seventeen women had retinopathy in grade 1–3. The retinopathy grade increased in nine women; remained unchanged in 17 women, and improved in three women. No women had or developed proliferative retinopathy (grade 4). The level of vitC in 1st trimester predicted the possible progression of retinopathy—the lower the vitC, the more probable the progression (p = 0.03; OR 1.6 (95% CI:1.06–3.2); n = 29 (multiple logistic regression))—while the combined levels of 1st and 2nd trimesters and the mean vitC level of the whole pregnancy did not. The diabetes duration, retinopathy grade per se in 1st trimester, 24-h blood pressure measurements, kidney function, urinary protein, HbA1c, or lipid profile were not independent predictors of progression of retinopathy during pregnancy. Retrospectively, the women who experienced progression of their retinopathy during and into postpartum had significantly lower vitC levels in 1st trimester (p = 0.02; n = 9/20), combined level of vitC in 1st and 2nd trimester (p = 0.032; n = 7/18), and mean vitC level of the whole pregnancy (p = 0.036; n = 7/9), respectively. In conclusion, our results suggest that low vitC status in pregnancy could be associated with progression of diabetic retinopathy. Full article

(This article belongs to the Special Issue Oxidative Stress, Pregnancy and Pregnancy-Related Diseases)

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16 pages, 1853 KiB

Open AccessArticle

Continuous Glucose Monitoring in Preterm Infants: The Role of Nutritional Management in Minimizing Glycemic Variability

by Valeria Musso, Isabella Panfoli, Marcella Battaglini, Giorgia Brigati, Diego Minghetti, Chiara Andreato and Luca A. Ramenghi

Antioxidants 2022, 11(10), 1945; https://doi.org/10.3390/antiox11101945 - 29 Sep 2022

Viewed by 1529

Abstract

Glycemic variability (GV) is common in preterm infants. In the premature population, GV is a risk factor for morbidity and mortality. Both hypo- and hyperglycemia can impair neurodevelopment. We investigated the impact of continuous versus intermittent tube enteral feeding on GV. In our [...] Read more.

Glycemic variability (GV) is common in preterm infants. In the premature population, GV is a risk factor for morbidity and mortality. Both hypo- and hyperglycemia can impair neurodevelopment. We investigated the impact of continuous versus intermittent tube enteral feeding on GV. In our prospective observational study, 20 preterm infants with a gestational age ≤ 34 weeks at either continuous or intermittent bolus full enteral feeding. For five days, continuous glucose monitoring (CGM) was utilized, which was achieved through the subcutaneous insertion of a sensor. A total of 27,532 measurements of blood glucose were taken. The mean amplitude of glycemic excursions did not differ between the two cohorts statistically. Continuous feeding resulted in higher positive values, increasing the risk of hypo- and hyperglycemia. Subjects who were small for their gestational age had a higher standard deviation during continuous feeding (p = 0.001). Data suggest that intermittent bolus nutrition is better for glycemic control than continuous nutrition. Nutritional management optimization of preterm infants appears to be critical for long-term health. In the future, CGM may provide a better understanding of the optimal glucose targets for various clinical conditions, allowing for a more personalized approach to management. Full article

(This article belongs to the Special Issue Oxidative Stress, Pregnancy and Pregnancy-Related Diseases)

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17 pages, 3719 KiB

Open AccessArticle

Chronic High-Altitude Hypoxia Alters Iron and Nitric Oxide Homeostasis in Fetal and Maternal Sheep Blood and Aorta

by Taiming Liu, Meijuan Zhang, Avoumia Mourkus, Hobe Schroeder, Lubo Zhang, Gordon G. Power and Arlin B. Blood

Antioxidants 2022, 11(9), 1821; https://doi.org/10.3390/antiox11091821 - 15 Sep 2022

Cited by 2 | Viewed by 1498

Abstract

The mammalian fetus thrives at oxygen tensions much lower than those of adults. Gestation at high altitude superimposes hypoxic stresses on the fetus resulting in increased erythropoiesis. We hypothesized that chronic hypoxia at high altitude alters the homeostasis of iron and bioactive nitric [...] Read more.

The mammalian fetus thrives at oxygen tensions much lower than those of adults. Gestation at high altitude superimposes hypoxic stresses on the fetus resulting in increased erythropoiesis. We hypothesized that chronic hypoxia at high altitude alters the homeostasis of iron and bioactive nitric oxide metabolites (NOx) in gestation. To test for this, electron paramagnetic resonance was used to provide unique measurements of iron, metalloproteins, and free radicals in the blood and aorta of fetal and maternal sheep from either high or low altitudes (3801 or 300 m). Using ozone-based chemiluminescence with selectivity for various NOx species, we determined the NOx levels in these samples immediately after collection. These experiments demonstrated a systemic redistribution of iron in high altitude fetuses as manifested by a decrease in both chelatable and total iron in the aorta and an increase in non-transferrin bound iron and total iron in plasma. Likewise, high altitude altered the redox status diversely in fetal blood and aorta. This study also found significant increases in blood and aortic tissue NOx in fetuses and mothers at high altitude. In addition, gradients in NOx concentrations observed between fetus and mother, umbilical artery and vein, and plasma and RBCs demonstrated complex dynamic homeostasis of NOx among these circulatory compartments, such as placental generation and efflux as well as fetal consumption of iron-nitrosyls in RBCs, probably HbNO. In conclusion, these results may suggest the utilization of iron from non-hematopoietic tissues iron for erythropoiesis in the fetus and increased NO bioavailability in response to chronic hypoxic stress at high altitude during gestation. Full article

(This article belongs to the Special Issue Oxidative Stress, Pregnancy and Pregnancy-Related Diseases)

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22 pages, 4532 KiB

Open AccessArticle

Oxidative and Inflammatory Imbalance in Placenta and Kidney of sFlt1-Induced Early-Onset Preeclampsia Rat Model

by Álvaro Santana-Garrido, Claudia Reyes-Goya, Pablo Espinosa-Martín, Luis Sobrevia, Luis M. Beltrán, Carmen M. Vázquez and Alfonso Mate

Antioxidants 2022, 11(8), 1608; https://doi.org/10.3390/antiox11081608 - 19 Aug 2022

Cited by 9 | Viewed by 2424

Abstract

Preeclampsia (PE) is a pregnancy-specific disorder characterized by the new onset of hypertension plus proteinuria and/or end-organ dysfunction. Here, we investigate the role of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase system as a major component of reactive oxygen species generation, in a [...] Read more.

Preeclampsia (PE) is a pregnancy-specific disorder characterized by the new onset of hypertension plus proteinuria and/or end-organ dysfunction. Here, we investigate the role of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase system as a major component of reactive oxygen species generation, in a rodent model of early-onset preeclampsia induced by excess sFlt1 (soluble fms-like tyrosine kinase 1). Placenta and kidney samples were obtained from normal pregnant and PE rats to measure the sFlt1/PlGF (placental growth factor) ratio in addition to oxidative stress-related parameters, including the activities and expressions of NADPH oxidase isoforms (NOX1, NOX2, and NOX4), components of nitric oxide (NO) metabolism, and antioxidant enzymes. Peroxisome proliferator-activated receptors (PPARα, PPARγ) and cytokines IL1β, IL3, IL6, IL10, and IL18 were also measured to evaluate the inflammation status in our experimental setting. Excessive O₂^●− production was found in rats that were treated with sFlt1; interestingly, this alteration appears to be mediated mainly by NOX2 in the placenta and by NOX4 in the kidney. Altered NO metabolism and antioxidant defense systems, together with mitochondrial dysfunction, were observed in this model of PE. Preeclamptic animals also exhibited overexpression of proinflammatory biomarkers as well as increased collagen deposition. Our results highlight the role of NADPH oxidase in mediating oxidative stress and possibly inflammatory processes in the placenta and kidney of an sFlt1-based model of early-onset preeclampsia. Full article

(This article belongs to the Special Issue Oxidative Stress, Pregnancy and Pregnancy-Related Diseases)

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13 pages, 857 KiB

Open AccessArticle

Pre-Treatment Physical Activity Could Positively Influence Pregnancy Rates in IVF despite the Induced Oxidative Stress: A Cohort Study on Salivary 8-Hydroxy-2′-deoxyguanosine

by Viktória Prémusz, Dominika Lendvai-Emmert, Alexandra Makai, Krisztina Amrein, Shalini Chauhan, József Bódis, Kálmán András Kovács and Ákos Várnagy

Antioxidants 2022, 11(8), 1586; https://doi.org/10.3390/antiox11081586 - 16 Aug 2022

Cited by 1 | Viewed by 1563

Abstract

(1) Background: This study was designed to define whether pretreatment habitual physical activity (PA)-induced oxidative stress (OS) influences outcome measures by using 8-hydroxy-2′-deoxyguanosine (8-OHdG) in saliva samples of patients undergoing in vitro fertilization (IVF). (2) Method: In this cohort study, samples were obtained [...] Read more.

(1) Background: This study was designed to define whether pretreatment habitual physical activity (PA)-induced oxidative stress (OS) influences outcome measures by using 8-hydroxy-2′-deoxyguanosine (8-OHdG) in saliva samples of patients undergoing in vitro fertilization (IVF). (2) Method: In this cohort study, samples were obtained from 26 patients (age: 34.6 ± 5.5 years, BMI: 25.3 ± 5.1, infertility: 51.0 ± 28.7 months) before the treatment and a follow-up of outcome measures of IVF/ICSI. The 8-OHdG was evaluated by Abcam’s ELISA (ab201734), PA patterns by GPAQ-H and ActiGraph GT3X; (3) Results: The number of matured oocytes was positively influenced by the GPAQ-H recreation MET (R² = 0.367, F = 10.994, p = 0.004; β = 0.005, p = 0.004, B Constant = 4.604) and a positive significant relationship (R² = 0.757, F = 17.692, p < 0.001, B Constant = 1.342) was found with GPAQ-H recreational PA MET (β = 0.004, p < 0.001), and Grade 1 embryos and higher very vigorous activity (GT3X) were accompanied (R² = 0.958, F = 408.479, p < 0.001) by higher ß-hCG levels (β = 63.703, p ≤ 0.001). Unanticipated positive correlation between 8-OHdG and ß-hCG level (R = 0.467, p = 0.028) was noticed, and there were significant differences in 8-OHdG in biochemical pregnancies (pregnant: 54.82 ± 35.56 ng/mL, non-pregnant: 30.06 ± 10.40 ng/mL, p = 0.022) as well. (4) Conclusions: Pretreatment PA could positively influence reproductive performance in IVF/ICSI despite the induced OS. However, a more sensitive biomarker and the recommended amount of activity should be further investigated. Full article

(This article belongs to the Special Issue Oxidative Stress, Pregnancy and Pregnancy-Related Diseases)

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16 pages, 1749 KiB

Open AccessArticle

Influence of Neonatal Sex on Breast Milk Protein and Antioxidant Content in Spanish Women in the First Month of Lactation

by David Ramiro-Cortijo, Andrea Gila-Diaz, Gloria Herranz Carrillo, Silvia Cañas, Alicia Gil-Ramírez, Santiago Ruvira, María A. Martin-Cabrejas and Silvia M. Arribas

Antioxidants 2022, 11(8), 1472; https://doi.org/10.3390/antiox11081472 - 28 Jul 2022

Cited by 2 | Viewed by 21701

Abstract

Breast milk (BM) is the best food for newborns. Male sex is associated with a higher risk of fetal programming, prematurity, and adverse postnatal outcome, being that BM is an important health determinant. BM composition is dynamic and modified by several factors, including [...] Read more.

Breast milk (BM) is the best food for newborns. Male sex is associated with a higher risk of fetal programming, prematurity, and adverse postnatal outcome, being that BM is an important health determinant. BM composition is dynamic and modified by several factors, including lactation period, prematurity, maternal nutritional status, and others. This study was designed to evaluate the influence of sex on BM composition during the first month of lactation, focused on macronutrients and antioxidants. Forty-eight breastfeeding women and their fifty-five newborns were recruited at the Hospital Clínico San Carlos (Madrid, Spain). Clinical sociodemographic data and anthropometric parameters were collected. BM samples were obtained at days 7, 14, and 28 of lactation to assess fat (Mojonnier method), protein (Bradford method), and biomarkers of oxidative status: total antioxidant capacity (ABTS and FRAP methods), thiol groups, reduced glutathione, superoxide dismutase and catalase activities, lipid peroxidation, and protein oxidation (spectrophotometric methods). Linear mixed models with random effects adjusted by maternal anthropometry, neonatal Z-scores at birth, and gestational age were used to assess the main effects of sex, lactation period, and their interaction. BM from mothers with male neonates exhibited significantly higher protein, ABTS, FRAP, and GSH levels, while catalase showed the opposite trend. No differences between sexes were observed in SOD, total thiols, and oxidative damage biomarkers. Most changes were observed on day 7 of lactation. Adjusted models demonstrated a significant association between male sex and proteins (β = 2.70 ± 1.20; p-Value = 0.048). In addition, total antioxidant capacity by ABTS (β = 0.11 ± 0.06) and GSH (β = 1.82 ± 0.94) showed a positive trend near significance (p-Value = 0.056; p-Value = 0.064, respectively). In conclusion, transitional milk showed sex differences in composition with higher protein and GSH levels in males. This may represent an advantage in the immediate perinatal period, which may help to counteract the worse adaptation of males to adverse intrauterine environments and prematurity. Full article

(This article belongs to the Special Issue Oxidative Stress, Pregnancy and Pregnancy-Related Diseases)

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10 pages, 1244 KiB

Open AccessArticle

Factors Involved in Endothelial Dysfunction Related to Angiogenic Disbalance and Oxidative Stress, in Women at High Risk of Term Pre-Eclampsia

by Jean Michell Santoyo, José Antonio Noguera, Francisco Avilés, Juan Luis Delgado, Catalina de Paco-Matallana, Virginia Pérez and Isabel Hernández

Antioxidants 2022, 11(7), 1409; https://doi.org/10.3390/antiox11071409 - 21 Jul 2022

Cited by 4 | Viewed by 1658

Abstract

Oxidative and inflammatory stress, angiogenic imbalance, and endothelial dysfunction are pathophysiological mechanisms occurring in pre-eclampsia (PE) that may persist over time and predispose women to a higher risk of cardiovascular disease (CVD) in the future. However, there is little evidence on the vascular [...] Read more.

Oxidative and inflammatory stress, angiogenic imbalance, and endothelial dysfunction are pathophysiological mechanisms occurring in pre-eclampsia (PE) that may persist over time and predispose women to a higher risk of cardiovascular disease (CVD) in the future. However, there is little evidence on the vascular function of women at risk of PE who have not developed the disease. The main objective of this research is to study factors and biomarkers involved in endothelial dysfunction related to oxidative stress, angiogenic disbalance, and inflammation in women at high risk of term PE who do not develop the disease. An observational, analytical, retrospective, and descriptive study was carried out in a selected sample of 68 high-risk and 57 non-risk of term PE participants in the STATIN study (FFIS/2016/02/ST EUDRACT No: 2016-005206-19). A significant increase in mean arterial pressure (MAP) levels and oxidative stress biomarkers (uric acid, homocysteine, and total serum antioxidant capacity) was found. Biomarkers of inflammation (interleukin-6 and growth differentiation factor 15) and endothelial function (asymmetric dimethylarginine) were significantly elevated in the group at risk of pre-eclampsia. A significative dependence relationship was also established between MAP and interleukin-6 and uric acid. These results suggest that women at high risk of term PE may represent pregnancies with pre-existing maternal risk factors for CVD, manifested by the own cardiovascular overload of pregnancy. A better understanding of maternal cardiovascular function in pregnancy would allow the improved prediction of CVD late in life in women. Full article

(This article belongs to the Special Issue Oxidative Stress, Pregnancy and Pregnancy-Related Diseases)

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10 pages, 546 KiB

Open AccessArticle

Oxidative Stress and Fetal Growth Restriction Set Up Earlier in Undernourished Sheep Twin Pregnancies: Prevention with Antioxidant and Nutritional Supplementation

by Víctor H. Parraguez, Francisco Sales, Oscar Peralta, Monica De los Reyes and Antonio Gonzalez-Bulnes

Antioxidants 2022, 11(7), 1287; https://doi.org/10.3390/antiox11071287 - 28 Jun 2022

Cited by 5 | Viewed by 1400

Abstract

Hypoxemia and oxidative stress, resulting in intrauterine growth restriction (IUGR) in undernourished twin sheep pregnancies, has been described in near-term studies. Our aim was to evaluate if the counteractive effects of maternal nutritional or antioxidant supplementation on the fetal redox status were evident [...] Read more.

Hypoxemia and oxidative stress, resulting in intrauterine growth restriction (IUGR) in undernourished twin sheep pregnancies, has been described in near-term studies. Our aim was to evaluate if the counteractive effects of maternal nutritional or antioxidant supplementation on the fetal redox status were evident before the accelerated fetal growth phase. Forty twin-bearing ewes grazing on natural Patagonian prairie were randomly assigned to four groups (n = 10 each; P: control ewes consuming mainly natural pasture; P+A: pasture plus antioxidants; P+C: pasture plus concentrate; P+A+C: pasture plus antioxidants and concentrate). Daily herbal antioxidants were supplemented in a feedstuff concentrate as a premix from day 35 until day 100 of gestation, when fetal venous cord blood samples and biometric measurements were obtained via cesarean section. The fetuses from group P were clearly hypoxemic. An analysis of variance showed that maternal antioxidant supplementation showed a trend of increased PO₂, SatHb, and Ht, effects not observed in P+C fetuses. Antioxidants decreased the fetal MDA concentration (p < 0.05). Fetal TAC was increased by the antioxidants and concentrate (p < 0.05). Antioxidant supplementation showed a trend to increase fetal body weight but not biometry. The results suggest that negative effects of oxidative stress occur earlier than the overt growth arrest, and the maternal administration of antioxidants may constitute a good nutritional strategy for the early prevention of IUGR. Full article

(This article belongs to the Special Issue Oxidative Stress, Pregnancy and Pregnancy-Related Diseases)

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17 pages, 2521 KiB

Open AccessArticle

The Effect of Tauroursodeoxycholic Acid (TUDCA) Treatment on Pregnancy Outcomes and Vascular Function in a Rat Model of Advanced Maternal Age

by Mazhar Pasha, Raven Kirschenman, Amy Wooldridge, Floor Spaans, Christy-Lynn M. Cooke and Sandra T. Davidge

Antioxidants 2022, 11(7), 1275; https://doi.org/10.3390/antiox11071275 - 28 Jun 2022

Cited by 5 | Viewed by 2678

Abstract

Advanced maternal age (≥35 years) increases the risk of vascular complications in pregnancy that can result in fetal growth restriction and preeclampsia. Endoplasmic reticulum (ER) stress has been linked to adverse pregnancy outcomes in these complicated pregnancies. However, the role of ER stress [...] Read more.

Advanced maternal age (≥35 years) increases the risk of vascular complications in pregnancy that can result in fetal growth restriction and preeclampsia. Endoplasmic reticulum (ER) stress has been linked to adverse pregnancy outcomes in these complicated pregnancies. However, the role of ER stress in advanced maternal age is not known. We hypothesize that increased ER stress contributes to altered vascular function and poor pregnancy outcomes, and that treatment with the ER-stress inhibitor TUDCA will improve pregnancy outcomes. First, young and aged non-pregnant/pregnant rats were used to assess ER stress markers in mesenteric arteries; mesenteric artery phospho-eIF2α and CHOP expression were increased in aged dams compared to young dams. In a second study, young and aged control and TUDCA-treated dams were studied on gestational day (GD) 20 (term = 22 days). TUDCA treatment was provided via the drinking water throughout pregnancy (GD0-GD20; calculated dose of 150 mg/kg/day TUDCA). ER stress markers were quantified in mesenteric arteries, blood pressure was measured, pregnancy outcomes were recorded, mesenteric and main uterine arteries were isolated and vascular function was assessed by wire myography. Aged dams had increased phospho-eIF2α and CHOP expression, reduced fetal weight, reduced litter size, and impaired uterine artery relaxation. In the aged dams, TUDCA treatment reduced phospho-eIF2α and CHOP expression, reduced blood pressure, improved fetal body weight, and tended to improve uterine artery function compared to control-treated aged dams. In conclusion, our data illustrate the role of ER stress, as well as TUDCA as a potential therapeutic that may benefit pregnancy outcomes in advanced maternal age. Full article

(This article belongs to the Special Issue Oxidative Stress, Pregnancy and Pregnancy-Related Diseases)

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17 pages, 1922 KiB

Open AccessArticle

Increased Circulating Levels of PCSK9 and Pro-Atherogenic Lipoprotein Profile in Pregnant Women with Maternal Supraphysiological Hypercholesterolemia

by Claudette Cantin, María Jesús Garchitorena, Rodrigo Escalona, Jorge A. Carvajal, Sebastián E. Illanes, Jaime Gutierrez and Andrea Leiva

Antioxidants 2022, 11(5), 869; https://doi.org/10.3390/antiox11050869 - 28 Apr 2022

Cited by 3 | Viewed by 1682

Abstract

Maternal physiological hypercholesterolemia (MPH) occurs during pregnancy to assure fetal development. Some pregnant women develop maternal supraphysiological hypercholesterolemia (MSPH) characterized by increased levels of low-density lipoprotein (LDL). We aim to determine if proprotein convertase subtilisin/kexin type 9 (PCSK9) levels (a protein that regulate [...] Read more.

Maternal physiological hypercholesterolemia (MPH) occurs during pregnancy to assure fetal development. Some pregnant women develop maternal supraphysiological hypercholesterolemia (MSPH) characterized by increased levels of low-density lipoprotein (LDL). We aim to determine if proprotein convertase subtilisin/kexin type 9 (PCSK9) levels (a protein that regulate the availability of LDL receptor in the cells surface), as well as the composition and function of LDL, are modulated in MSPH women. This study included 122 pregnant women. Maternal total cholesterol (TC), LDL, triglycerides and PCSK9 increased from first (T1) to third trimester (T3) in MPH women. At T3, maternal TC, LDL, PCSK9 and placental abundances of PCSK9 were significantly higher in MPSH compared to MPH. Circulating PCSK9 levels were correlated with LDL at T3. In MSPH women, the levels of lipid peroxidation and oxidized LDL were significantly higher compared to MPH. LDL isolated from MSPH women presented significantly higher triglycerides and ApoB but lower levels of ApoAI compared to MPH. The formation of conjugated dienes was earlier in LDL from MSPH and in endothelial cells incubated with these LDLs; the levels of reactive oxygen species were significantly higher compared to LDL from MPH. We conclude that increased maternal PCSK9 would contribute to the maternal elevated levels of pro-atherogenic LDL in MSPH, which could eventually be related to maternal vascular dysfunction. Full article

(This article belongs to the Special Issue Oxidative Stress, Pregnancy and Pregnancy-Related Diseases)

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16 pages, 890 KiB

Open AccessArticle

Vitamin D Deficiency, Excessive Gestational Weight Gain, and Oxidative Stress Predict Small for Gestational Age Newborns Using an Artificial Neural Network Model

by Otilia Perichart-Perera, Valeria Avila-Sosa, Juan Mario Solis-Paredes, Araceli Montoya-Estrada, Enrique Reyes-Muñoz, Ameyalli M. Rodríguez-Cano, Carla P. González-Leyva, Maribel Sánchez-Martínez, Guadalupe Estrada-Gutierrez and Claudine Irles

Antioxidants 2022, 11(3), 574; https://doi.org/10.3390/antiox11030574 - 17 Mar 2022

Cited by 4 | Viewed by 2863

Abstract

(1) Background: Size at birth is an important early determinant of health later in life. The prevalence of small for gestational age (SGA) newborns is high worldwide and may be associated with maternal nutritional and metabolic factors. Thus, estimation of fetal growth is [...] Read more.

(1) Background: Size at birth is an important early determinant of health later in life. The prevalence of small for gestational age (SGA) newborns is high worldwide and may be associated with maternal nutritional and metabolic factors. Thus, estimation of fetal growth is warranted. (2) Methods: In this work, we developed an artificial neural network (ANN) model based on first-trimester maternal body fat composition, biochemical and oxidative stress biomarkers, and gestational weight gain (GWG) to predict an SGA newborn in pregnancies with or without obesity. A sensibility analysis to classify maternal features was conducted, and a simulator based on the ANN algorithm was constructed to predict the SGA outcome. Several predictions were performed by varying the most critical maternal features attained by the model to obtain different scenarios leading to SGA. (3) Results: The ANN model showed good performance between the actual and simulated data (R² = 0.938) and an AUROC of 0.8 on an independent dataset. The top-five maternal predictors in the first trimester were protein and lipid oxidation biomarkers (carbonylated proteins and malondialdehyde), GWG, vitamin D, and total antioxidant capacity. Finally, excessive GWG and redox imbalance predicted SGA newborns in the implemented simulator. Significantly, vitamin D deficiency also predicted simulated SGA independently of GWG or redox status. (4) Conclusions: The study provided a computational model for the early prediction of SGA, in addition to a promising simulator that facilitates hypothesis-driven constructions, to be further validated as an application. Full article

(This article belongs to the Special Issue Oxidative Stress, Pregnancy and Pregnancy-Related Diseases)

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24 pages, 5286 KiB

Open AccessArticle

Dysregulated Autophagy Leads to Oxidative Stress and Aberrant Expression of ABC Transporters in Women with Early Miscarriage

by Saira Shahnawaz, Usman Shah Nawaz, Jonas Zaugg, Ghulam Hussain, Nadia Malik, Muhammad Zahoor-ul-Hassan Dogar, Shoaib Ahmad Malik and Christiane Albrecht

Antioxidants 2021, 10(11), 1742; https://doi.org/10.3390/antiox10111742 - 30 Oct 2021

Cited by 8 | Viewed by 2868

Abstract

Early miscarriage (EMC) is a devastating obstetrical complication. ATP-binding cassette (ABC) transporters mediate cholesterol transfer across the placenta and enhance cell survival by effluxing substrates from target cells in the presence of stressors. Recent evidence reports an intricate interplay between autophagy and ABC [...] Read more.

Early miscarriage (EMC) is a devastating obstetrical complication. ATP-binding cassette (ABC) transporters mediate cholesterol transfer across the placenta and enhance cell survival by effluxing substrates from target cells in the presence of stressors. Recent evidence reports an intricate interplay between autophagy and ABC transporters. We hypothesized that dysregulated autophagy and oxidative stress (OS) in the placenta leads to abnormal expression of membrane transporters contributing to poor pregnancy survival in EMC. We determined mRNA and protein expression of autophagy genes (Beclin-1/Bcl-2/LC3I/LC3II/p62) and ABC transporters (ABCA1/ABCG1/ABCG2) in placentae from EMC patients (n = 20), term controls (n = 19), first trimester (n = 6), and term controls (n = 5) controls. Oxidative/antioxidant status and biomarkers of oxidative damage were evaluated in maternal serum and placentae from EMC and healthy controls. In EMC, placental expression of LC3II/LC3I as well as of the key autophagy regulatory proteins Beclin-1 and Bcl-2 were reduced, whereas p62 was increased. Both in the serum and placentae of EMC patients, total OS was elevated reflected by increased oxidative damage markers (8-OHdG/malondialdehyde/carbonyl formation) accompanied by diminished levels of total antioxidant status, catalase, and total glutathione. Furthermore, we found reduced ABCG1 and increased ABCG2 expression. These findings suggest that a decreased autophagy status triggers Bcl-2-dependent OS leading to macromolecule damage in EMC placentae. The decreased expression of ABCG1 contributes to reduced cholesterol export to the growing fetus. Increasing ABCG2 expression could represent a protective feedback mechanism under inhibited autophagy conditions. In conclusion, dysregulated autophagy combined with increased oxidative toxicity and aberrant expression of placental ABC transporters affects materno-fetal health in EMC. Full article

(This article belongs to the Special Issue Oxidative Stress, Pregnancy and Pregnancy-Related Diseases)

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14 pages, 1608 KiB

Open AccessArticle

Mitochondrial and Oxidative Unbalance in Placentas from Mothers with SARS-CoV-2 Infection

by Chiara Mandò, Valeria M. Savasi, Gaia M. Anelli, Silvia Corti, Anaïs Serati, Fabrizia Lisso, Chiara Tasca, Chiara Novielli and Irene Cetin

Antioxidants 2021, 10(10), 1517; https://doi.org/10.3390/antiox10101517 - 24 Sep 2021

Cited by 14 | Viewed by 2695

Abstract

SARS-CoV-2 infection has been related to adverse pregnancy outcomes. A placental role in protecting the fetus from SARS-CoV-2 infection has been documented. Nevertheless, it is still unclear how the placenta is affected in SARS-CoV-2 infection. Here we assessed placental mitochondrial (mt) and oxidative [...] Read more.

SARS-CoV-2 infection has been related to adverse pregnancy outcomes. A placental role in protecting the fetus from SARS-CoV-2 infection has been documented. Nevertheless, it is still unclear how the placenta is affected in SARS-CoV-2 infection. Here we assessed placental mitochondrial (mt) and oxidative features in COVID-19 and healthy mothers. mtDNA levels, DNA oxidative damage, expression levels of genes involved in antioxidant defenses, mitochondrial dynamics and respiratory chain subunits were investigated in placentas from singleton pregnancies of 30 women with SARS-CoV-2 infection during the third trimester (12 asymptomatic, 18 symptomatic) and 16 controls. mtDNA levels decreased in COVID-19 placentas vs. controls and inversely correlated with DNA oxidative damage, which increased in the symptomatic group. Antioxidant gene expressions decreased in SARS-CoV-2 mothers (CAT, GSS). Symptomatic cases also showed a lower expression of respiratory chain (NDUFA9, SDHA, COX4I1) and mt dynamics (DNM1L, FIS1) genes. Alterations in placental mitochondrial features and oxidative balance in COVID-19-affected mothers might be due to the impaired intrauterine environment, generated by systemic viral effects, leading to a negative vicious circle that worsens placental oxidative stress and mitochondrial efficiency. This likely causes cell homeostasis dysregulations, raising the potential of possible long-term effects. Full article

(This article belongs to the Special Issue Oxidative Stress, Pregnancy and Pregnancy-Related Diseases)

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Review

Jump to: Research

19 pages, 633 KiB

Open AccessReview

Markers of Oxidative Stress in Obstetrics and Gynaecology—A Systematic Literature Review

by Michalina Anna Drejza, Katarzyna Rylewicz, Ewa Majcherek, Katarzyna Gross-Tyrkin, Małgorzata Mizgier, Katarzyna Plagens-Rotman, Małgorzata Wójcik, Katarzyna Panecka-Mysza, Magdalena Pisarska-Krawczyk, Witold Kędzia and Grażyna Jarząbek-Bielecka

Antioxidants 2022, 11(8), 1477; https://doi.org/10.3390/antiox11081477 - 28 Jul 2022

Cited by 8 | Viewed by 2748

Abstract

Oxidative stress has been implicated in many diseases, including reproductive and pregnancy disorders, from subfertility to maternal vascular disease or preterm labour. There is, however, discrepancy within the standardized markers of oxidative stress in obstetrics and gynaecology in clinical studies. This review aims [...] Read more.

Oxidative stress has been implicated in many diseases, including reproductive and pregnancy disorders, from subfertility to maternal vascular disease or preterm labour. There is, however, discrepancy within the standardized markers of oxidative stress in obstetrics and gynaecology in clinical studies. This review aims to present the scope of markers used between 2012 and 2022 to describe oxidative stress with regard to reproduction, pregnancy, and pregnancy-related issues. Despite the abundance of evidence, there is no consensus on the set of standardised markers of oxidative stress which poses a challenge to achieve universal consensus in order to appropriately triangulate the results. Full article

(This article belongs to the Special Issue Oxidative Stress, Pregnancy and Pregnancy-Related Diseases)

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10 pages, 309 KiB

Open AccessReview

Visceral Therapy and Physical Activity for Selected Dysfunctions, with Particular Emphasis on Locomotive Organ Pain in Pregnant Women—Importance of Reducing Oxidative Stress

by Małgorzata Wójcik, Grażyna Jarząbek-Bielecka, Piotr Merks, Dawid Luwański, Katarzyna Plagens-Rotman, Magdalena Pisarska-Krawczyk, Małgorzata Mizgier and Witold Kędzia

Antioxidants 2022, 11(6), 1118; https://doi.org/10.3390/antiox11061118 - 05 Jun 2022

Cited by 6 | Viewed by 3205

Abstract

Movement is a physiological phenomenon and a fundamental aspect of the living human body in a global context (e.g., musculoskeletal system function) and local one (e.g., visceral system function). The local activity of the body is expressed in the rhythm of pulsations, peristalsis [...] Read more.

Movement is a physiological phenomenon and a fundamental aspect of the living human body in a global context (e.g., musculoskeletal system function) and local one (e.g., visceral system function). The local activity of the body is expressed in the rhythm of pulsations, peristalsis and vibrations. Visceral therapy supports movement, articulation and tissue rhythm. The use of visceral treatment for pain is complementary and is relevant for pregnant women. Maintaining the mobility and motility of internal organs by means of visceral techniques can regulate anatomical relations and physiological processes within the urogenital diaphragm. The role of physical activity is also important. A scoping review was conducted to analyze the relevant literature on pain in pregnant women, the role of visceral therapy in pregnant women and oxidative stress. Eligible articles presented aspects of the occurrence of pain in locomotive organs in pregnant women, the use of visceral therapy in pain management, and the reduction of oxidative stress. The use of visceral therapy and physical activity in the treatment of pain is complementary and also important for pregnant women, and so may have an effect on reducing oxidative stress in pregnant women. Full article

(This article belongs to the Special Issue Oxidative Stress, Pregnancy and Pregnancy-Related Diseases)

15 pages, 919 KiB

Open AccessReview

Human Placental Intracellular Cholesterol Transport: A Focus on Lysosomal and Mitochondrial Dysfunction and Oxidative Stress

by Maria Jose Yañez and Andrea Leiva

Antioxidants 2022, 11(3), 500; https://doi.org/10.3390/antiox11030500 - 04 Mar 2022

Cited by 8 | Viewed by 3033

Abstract

The placenta participates in cholesterol biosynthesis and metabolism and regulates exchange between the maternal and fetal compartments. The fetus has high cholesterol requirements, and it is taken up and synthesized at elevated rates during pregnancy. In placental cells, the major source of cholesterol [...] Read more.

The placenta participates in cholesterol biosynthesis and metabolism and regulates exchange between the maternal and fetal compartments. The fetus has high cholesterol requirements, and it is taken up and synthesized at elevated rates during pregnancy. In placental cells, the major source of cholesterol is the internalization of lipoprotein particles from maternal circulation by mechanisms that are not fully understood. As in hepatocytes, syncytiotrophoblast uptake of lipoprotein cholesterol involves lipoprotein receptors such as low-density lipoprotein receptor (LDLR) and scavenger receptor class B type I (SR-BI). Efflux outside the cells requires proteins such as the ATP-binding cassette (ABC) transporters ABCA1 and ABCG1. However, mechanisms associated with intracellular traffic of cholesterol in syncytiotrophoblasts are mostly unknown. In hepatocytes, uptaken cholesterol is transported to acidic late endosomes (LE) and lysosomes (LY). Proteins such as Niemann–Pick type C 1 (NPC1), NPC2, and StAR related lipid transfer domain containing 3 (STARD3) are required for cholesterol exit from the LE/LY. These proteins transfer cholesterol from the lumen of the LE/LY into the LE/LY-limiting membrane and then export it to the endoplasmic reticulum, mitochondria, or plasma membrane. Although the production, metabolism, and transport of cholesterol in placental cells are well explored, there is little information on the role of proteins related to intracellular cholesterol traffic in placental cells during physiological or pathological pregnancies. Such studies would be relevant for understanding fetal and placental cholesterol management. Oxidative stress, induced by generating excess reactive oxygen species (ROS), plays a critical role in regulating various cellular and biological functions and has emerged as a critical common mechanism after lysosomal and mitochondrial dysfunction. This review discusses the role of cholesterol, lysosomal and mitochondrial dysfunction, and ROS in the development and progression of hypercholesterolemic pregnancies. Full article

(This article belongs to the Special Issue Oxidative Stress, Pregnancy and Pregnancy-Related Diseases)

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39 pages, 2768 KiB

Open AccessEditor’s ChoiceReview

Gestational Diabetes Mellitus: The Crosslink among Inflammation, Nitroxidative Stress, Intestinal Microbiota and Alternative Therapies

by Elaine Luiza Santos Soares de Mendonça, Marilene Brandão Tenório Fragoso, Jerusa Maria de Oliveira, Jadriane Almeida Xavier, Marília Oliveira Fonseca Goulart and Alane Cabral Menezes de Oliveira

Antioxidants 2022, 11(1), 129; https://doi.org/10.3390/antiox11010129 - 07 Jan 2022

Cited by 34 | Viewed by 10711

Abstract

Gestational diabetes mellitus (GDM) is characterized by a set of metabolic complications arising from adaptive failures to the pregnancy period. Estimates point to a prevalence of 3 to 15% of pregnancies. Its etiology includes intrinsic and extrinsic aspects of the progenitress, which may [...] Read more.

Gestational diabetes mellitus (GDM) is characterized by a set of metabolic complications arising from adaptive failures to the pregnancy period. Estimates point to a prevalence of 3 to 15% of pregnancies. Its etiology includes intrinsic and extrinsic aspects of the progenitress, which may contribute to the pathophysiogenesis of GDM. Recently, researchers have identified that inflammation, oxidative stress, and the gut microbiota participate in the development of the disease, with potentially harmful effects on the health of the maternal-fetal binomial, in the short and long terms. In this context, alternative therapies were investigated from two perspectives: the modulation of the intestinal microbiota, with probiotics and prebiotics, and the use of natural products with antioxidant and anti-inflammatory properties, which may mitigate the endogenous processes of the GDM, favoring the health of the mother and her offspring, and in a future perspective, alleviating this critical public health problem. Full article

(This article belongs to the Special Issue Oxidative Stress, Pregnancy and Pregnancy-Related Diseases)

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