The nuclear factor erythroid 2-related factor 2 (NRF2) is a transcription factor that plays a critical role in the xenobiotic and stress responses. During viral infection, NRF2 can modulate the host ...metabolism and innate immunity; however, the most common activity of NRF2 in viral diseases is controlling reactive oxygen species (ROS). The Zika virus (ZIKV) is involved in a vertical infection in pregnancy, with reported fetal health consequences. However, the possibility that ZIKV regulates NRF2 expression in placental trophoblasts has not been investigated. In this report, we evaluated the upregulation of NRF2 and antioxidant enzymes in a trophoblast-like cell. These findings could help us understand the antioxidant mechanism underlying the ZIKV infection in the placenta during pregnancy.
Endothelial dysfunction (ED) in preeclampsia (PE) results from the convergence of oxidative stress, inflammation, and alterations in extracellular matrix components, affecting vascular tone and ...permeability. The molecular network leading to ED includes IL-8 and MMP-2. In vitro, IL-8 regulates the concentration and activity of MMP-2 in the trophoblast; this interaction has not been studied in endothelial cells during PE. We isolated human umbilical vein endothelial cells (HUVECs) from women with healthy pregnancies (NP,
= 15) and PE (
= 15). We quantified the intracellular concentration of nitric oxide and reactive oxygen species with colorimetric assays, IL-8 with ELISA, and MMP-2 with zymography and using an ELISA-type system. An IL-8 inhibition assay was used to study the influence of this cytokine on MMP-2 concentration and activity. HUVECs from women with PE showed significantly higher oxidative stress than NP. IL-8 and MMP-2 were found to be significantly elevated in PE HUVECs compared to NP. Inhibition of IL-8 in HUVECs from women with PE significantly decreased the concentration of MMP-2. We demonstrate that IL-8 is involved in the mechanisms of MMP-2 expression in HUVECs from women with PE. Our findings provide new insights into the molecular mechanisms regulating the ED distinctive of PE.
Polycystic ovary syndrome (PCOS) is an endocrine disease associated with infertility and metabolic disorders in reproductive-aged women. In this study, we evaluated the expression of eight genes ...related to endometrial function and their DNA methylation levels in the endometrium of PCOS patients and women without the disease (control group). In addition, eight of the PCOS patients underwent intervention with metformin (1500 mg/day) and a carbohydrate-controlled diet (type and quantity) for three months. Clinical and metabolic parameters were determined, and RT-qPCR and MeDIP-qPCR were used to evaluate gene expression and DNA methylation levels, respectively. Decreased expression levels of
,
, and
genes and increased DNA methylation levels of the
promoter were found in the endometrium of PCOS patients compared to controls. After metformin and nutritional intervention, some metabolic and clinical variables improved in PCOS patients. This intervention was associated with increased expression of
,
, and
genes and reduced DNA methylation levels of the
promoter in the endometrium of PCOS women. Our preliminary findings suggest that metformin and a carbohydrate-controlled diet improve endometrial function in PCOS patients, partly by modulating DNA methylation of the
gene promoter and the expression of genes implicated in endometrial receptivity and insulin signaling.
Oxidative stress (OS) induced by SARS-CoV-2 infection may play an important role in COVID-19 complications. However, information on oxidative damage in pregnant women with COVID-19 is limited. ...Objective: We aimed to compare lipid and protein oxidative damage and total antioxidant capacity (TAC) between pregnant women with severe and non-severe COVID-19. Methods: We studied a consecutive prospective cohort of patients admitted to the obstetrics emergency department. All women positive for SARS-CoV-2 infection by reverse transcription-polymerase chain reaction (RT-qPCR) were included. Clinical data were collected and blood samples were obtained at hospital admission. Plasma OS markers, malondialdehyde (MDA), carbonylated proteins (CP), and TAC; angiogenic markers, fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF); and renin-angiotensin system (RAS) markers, angiotensin-converting enzyme 2 (ACE-2) and angiotensin-II (ANG-II) were measured. Correlation between OS, angiogenic, and RAS was evaluated. Results: In total, 57 pregnant women with COVID-19 were included, 17 (28.9%) of which had severe COVID-19; there were 3 (5.30%) maternal deaths. Pregnant women with severe COVID-19 had higher levels of carbonylated proteins (5782 pmol vs. 6651 pmol; p = 0.024) and total antioxidant capacity (40.1 pmol vs. 56.1 pmol; p = 0.001) than women with non-severe COVID-19. TAC was negatively correlated with ANG-II (p < 0.0001) and MDA levels (p < 0.0001) and positively with the sFlt-1/PlGF ratio (p = 0.027). Conclusions: In pregnant women, severe COVID-19 is associated with an increase in protein oxidative damage and total antioxidant capacity as a possible counterregulatory mechanism.
Introduction and Objective: The weight gained during pregnancy could determine the immediate and future health of the mother-child dyad. Excessive gestational weight gain (EGWG) due to abnormal ...adipose tissue (AT) accumulation is strongly associated with adverse perinatal outcomes as gestational diabetes, macrosomia, obesity, and hypertension further in life. Dysregulation of adipokine, AT dysfunction, and an imbalance in the prooxidant-antioxidant systems are critical features in altered AT accumulation. This study was aimed to investigate the association between adipokines and oxidative stress markers in pregnant women and the influence of the GWG on this association. Methods: Maternal blood samples were obtained in the third trimester of pregnancy (n = 74) and serum adipokines (adiponectin, leptin, and resistin), oxidative damage markers: 8-oxo-2′-deoxyguanosine (8-oxodG), lipohydroperoxides (LOOH), malondialdehyde (MDA), and carbonylated proteins (CP), and glucose a metabolic marker were measured. Results: Women with EGWG had low adiponectin levels than women with adequate weight gain (AWG) or insufficient weight gain (IWG). Multiple linear regression models revealed a positive association between adiponectin and 8-oxodG in women with AWG (B = 1.09, 95% CI: 164–222, p = 0.027) and IWG (B = 0.860, 95% CI: 0.199–1.52, p = 0.013) but not in women with EGWG. In women with EGWG, leptin was positively associated with LOOH (p = 0.018), MDA (p = 0.005), and CP (p = 0.010) oxidative markers. Conclusion: Our findings suggest that concurrent mechanisms regulate adipokine production and oxidative stress in pregnant women and that this regulation is influenced by GWG, probably due to an excessive AT accumulation.
Worldwide, diabetes mellitus represents a growing health problem. If it occurs during pregnancy, it can increase the risk of various abnormalities in early and advanced life stages of exposed ...individuals due to fetal programming occurring in utero. Studies have determined that maternal conditions interfere with the genotypes and phenotypes of offspring. Researchers are now uncovering the mechanisms by which epigenetic alterations caused by diabetes affect the expression of genes and, therefore, the development of various diseases. Among the numerous possible epigenetic changes in this regard, the most studied to date are DNA methylation and hydroxymethylation, as well as histone acetylation and methylation. This review article addresses critical findings in epigenetic studies involving diabetes mellitus, including variations reported in the expression of specific genes and their transgenerational effects.
The aim of this study was to examine the efficacy of intensive medical nutrition therapy (MNT) plus metformin in preventing gestational diabetes mellitus (GDM) among high-risk Mexican women. An ...open-label randomized clinical trial was conducted. Inclusion criteria were pregnant women with three or more GDM risk factors: Latino ethnic group, maternal age >35 years, body mass index >25 kg/m
, insulin resistance, and a history of previous GDM, prediabetes, a macrosomic neonate, polycystic ovarian syndrome, or a first-degree relative with type 2 diabetes. Women before 15 weeks of gestation were assigned to group 1 (
= 45): intensive MNT-plus metformin (850 mg twice/day) or group 2 (
= 45): intensive MNT without metformin. Intensive MNT included individual dietary counseling, with ≤50% of total energy from high carbohydrates. The primary outcome was the GDM incidence according to the International Association of Diabetes Pregnancy Study Groups criteria. There were no significant differences in baseline characteristics and adverse perinatal outcomes between the groups. The GDM incidence was
= 11 (24.4%) in the MNT plus metformin group versus
= 7 (15.5%) in the MNT without metformin group:
= 0.42 (RR: 1.57 95% CI: 0.67-3.68). There is no benefit in adding metformin to intensive MNT to prevent GDM among high-risk Mexican women. Clinical trials registration: NCT01675310.
Age-adjusted rates of cardiovascular disease (CVD) are higher in men than in women. CVD risk-factor outcomes are underrecognized, underestimated, and undertreated in women because the clinical ...expressions in women differ from those of men. There are no universally accepted recommendations on what to do in women when the values of fasting glucose, blood pressure, and lipids are only slightly altered or at borderline values. We reported the positive effects on CVD risk markers using cacao by-products, showing that alternative approaches can be used to prevent cardiovascular disease in women. The objective was to evaluate the changes in lipoprotein subfractions induced by three months of treatment with an epicatechin-enriched cacao supplement.
A double-blind, placebo-controlled proof-of-concept study was developed to evaluate the effects of 3 months of treatment with an (-)-epicatechin-enriched cacao supplement on lipoprotein subfractions.
The usual screening workshop for postmenopausal women could be insufficient and misleading. Assessing the effect of a (-)-epicatechin-enriched cacao supplement employing a lipoprotein subfractionation profile analysis suggests a decrease in cardiovascular risk.
A simple, low-cost, safe (-)-epicatechin-enriched cacao supplement product can improve the cardiovascular risk in postmenopausal women.
Maternal obesity has been related to adverse neonatal outcomes and fetal programming. Oxidative stress and adipokines are potential biomarkers in such pregnancies; thus, the measurement of these ...molecules has been considered critical. Therefore, we developed artificial neural network (ANN) models based on maternal weight status and clinical data to predict reliable maternal blood concentrations of these biomarkers at the end of pregnancy. Adipokines (adiponectin, leptin, and resistin), and DNA, lipid and protein oxidative markers (8-oxo-2'-deoxyguanosine, malondialdehyde and carbonylated proteins, respectively) were assessed in blood of normal weight, overweight and obese women in the third trimester of pregnancy. A Back-propagation algorithm was used to train ANN models with four input variables (age, pre-gestational body mass index (p-BMI), weight status and gestational age). ANN models were able to accurately predict all biomarkers with regression coefficients greater than R² = 0.945. P-BMI was the most significant variable for estimating adiponectin and carbonylated proteins concentrations (37%), while gestational age was the most relevant variable to predict resistin and malondialdehyde (34%). Age, gestational age and p-BMI had the same significance for leptin values. Finally, for 8-oxo-2'-deoxyguanosine prediction, the most significant variable was age (37%). These models become relevant to improve clinical and nutrition interventions in prenatal care.
Ultra-processed food (UPF) consumption during gestation may lead to increased oxidative stress (OS) and could affect pregnancy outcomes. This study aims to evaluate the association of UPF consumption ...during pregnancy with circulating levels of OS markers. Diet was assessed (average of three assessments) in 119 pregnant women enrolled in the OBESO perinatal cohort (Mexico), obtaining quantitative data and the percentage of energy that UPFs (NOVA) contributed to the total diet. Sociodemographic, clinical (pregestational body-mass index and gestational weight gain) and lifestyle data were collected. Maternal circulating levels of OS markers (malondialdehyde (MDA), protein carbonylation (PC), and total antioxidant capacity (TAC)) were determined at the third trimester of pregnancy. Adjusted linear regression models were performed to analyze the association between UPFs and OS markers. UPFs represented 27.99% of the total energy intake. Women with a lower UPF consumption (<75 percentile°) presented a higher intake of fiber, ω-3, ω-6, and a lower ω-6/3 ratio. Linear regression models showed that UPFs were inversely associated with TAC and MDA. Fiber intake was associated with PC. UPF intake during pregnancy may result in an increase in oxidative stress. When providing nutrition care, limiting or avoiding UPFs may be an intervention strategy that could promote a better antioxidant capacity in the body.
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