Regulation of MMP-2 by IL-8 in Vascular Endothelial Cells: Probable Mechanism for Endothelial Dysfunction in Women with Preeclampsia.

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, n = 15) and PE (n = 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.

The Effect of Metformin and Carbohydrate-Controlled Diet on DNA Methylation and Gene Expression in the Endometrium of Women with Polycystic Ovary Syndrome.

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 HOXA10, GAB1, and SLC2A4 genes and increased DNA methylation levels of the HOXA10 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 HOXA10, ESR1, GAB1, and SLC2A4 genes and reduced DNA methylation levels of the HOXA10 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 HOXA10 gene promoter and the expression of genes implicated in endometrial receptivity and insulin signaling.

Hyperglycemia affects neuronal differentiation and Nestin, FOXO1, and LMO3 mRNA expression of human Wharton's jelly mesenchymal stem cells of children from diabetic mothers.

Pregestational Diabetes Mellitus (PDM) during pregnancy constitutes an unfavorable embryonic and fetal development environment, with a high incidence of congenital malformations (CM). Neural tube defects are the second most common type of CM in children of diabetic mothers (CDM), who also have an elevated risk of developing neurodevelopmental disorders. The mechanisms that lead to these neuronal disorders in CDM are not yet fully understood. The present study aimed to know the effect of hyperglycemia on proliferation, neuronal differentiation percentage, and expression of neuronal differentiation mRNA markers in human umbilical cord Wharton's jelly mesenchymal stem cells (hUCWJMSC) of children from normoglycemic pregnancies (NGP) and PDM. We isolated and characterized hUCWJMSC by flow cytometry, immunofluorescence, RT-PCR and were induced to differentiate into adipocytes, osteocytes, and neurons. Proliferation assays were performed to determine the doubling time, and Nestin, TUBB3, FOXO1, KCNK2, LMO3, and MAP2 mRNA gene expression was assessed by semiquantitative RT-PCR. Hyperglycemia significantly decreased proliferation and neuronal differentiation percentage in NGP and PDM cells treated with 40 mM d-glucose. Nestin mRNA expression decreased under control glycemic conditions, while FOXO1, KCNK2, LMO3, and MAP2 mRNA expression increased during neuronal differentiation in both NGP and PDM cells. On the other hand, under hyperglycemic conditions, Nestin was significantly decreased in cells from NGP but not in cells from PDM, while mRNA expression of FOXO1 and LMO3 was significantly increased in cells from NGP, but not in cells from PDM. We found evidence that maternal PDM, with hyperglycemia in culture, affects the biological properties of fetal cells. All these results could be part of fetal programming.

Markers of oxidative stress in postmenopausal women with metabolic syndrome.

During the postmenopausal period, there are metabolic alterations that predispose individuals to metabolic syndrome (MS), oxidative stress (OS), and the risk of developing cardiovascular diseases. We aimed to compare the concentrations of OS markers in postmenopausal women with and without MS. Malondialdehyde, carbonyl groups, and total antioxidant capacity (TAC) were quantified. We conducted a cross-sectional study: Group 1 (n = 42) included women without MS, and Group 2 (n = 58) comprised women with MS. Participants' age was similar between groups. Glucose, insulin, the homeostasis model assessment of insulin resistance, triglycerides, uric acid, and body mass index were significantly lower in postmenopausal women without MS. OS markers were significantly lower in Group 1 vs. Group 2: malondialdehyde, 31.32 ± 14.93 vs. 40.27 ± 17.62 pmol MDA/mg dry weight (p = .01); protein carbonylation, 6325 ± 1551 vs. 7163 ± 1029 pmol PC/mg protein (p = .0003); and TAC, 1497 ± 297.3 vs. 1619 ± 278.8 pmol Trolox equivalent/mg protein (p = .041). OS markers were significantly higher in postmenopausal women with MS. Impact statementWhat is already known on this subject? Oxidative stress has been implicated in numerous disease processes; however, information on the relationship between oxidative stress and metabolic syndrome among postmenopausal women remains limited.What do the results of this study add? Our results indicate that in postmenopausal Mexican women, oxidative stress markers were significantly lower in those without metabolic syndrome, whereas total antioxidant capacity was higher in those with metabolic syndrome, which could be explained as an antioxidant defense mechanism capable of neutralising excess oxidative damage markers.What are the implications of these findings for clinical practice and/or further research? This study is of interest to a broad audience because it compares the concentrations of oxidative stress markers in postmenopausal women with and without metabolic syndrome. Our study could support intervention with supplements or foods rich in antioxidants as lifestyle modifications in postmenopausal women with metabolic syndrome.

Prevalence of Thyroid Autoimmunity in Women with Recurrent Pregnancy Loss.

Background and objectives: Thyroid autoimmunity (TAI) has been associated with a significantly increased risk of miscarriage in women with recurrent pregnancy loss (RPL). The aim of this study was to determine the prevalence of TAI in women with RPL and compare the clinical characteristics of positive and negative TAI women. Materials and Methods: This is a retrospective cross-sectional study; 203 women with RPL were included. Thyroid profile, anti-thyroid peroxidase (TPO-Ab), and anti-thyroglobulin (TG-Ab) antibodies were measured in all participants. Clinical characteristics and causes of RPL were compared between positive and negative TAI. Results: Prevalence of TAI was 14.8%; prevalence of positive TPO-Ab and TG-Ab was 12.3% and 4.9%, respectively. Women with TAI had significantly higher concentrations of thyrotropin (TSH) compared to women without TAI (4.8 ± 3.8 versus 3.1 ± 1.1, p = 0.001). There was no significant difference in age, the number of gestations, miscarriages, state of antiphospholipid antibodies (aPL), or causes of RPL between women that were TAI-positive versus TAI-negative. Prevalence of positive TAI by cause of RPL was: endocrine 7/25 (28%), genetic 1/5 (20%), autoimmune 1/5 (20%), anatomic 8/55 (14.5%), and unexplained cause 13/112 (11.6%). Conclusions: The prevalence of TAI in women with RPL is 14.8%. Women with an endocrine cause have the highest prevalence of TAI.

Is gestational diabetes mellitus in obese women predicted by oxidative damage in red blood cells?

Obesity in pregnant women has been associated with an increased risk of maternal complications, including gestational diabetes mellitus (GDM), a process that is related to oxidative stress (OS). To evaluate the biomarkers of OS in red blood cells (RBCs), we assigned 80 pregnant women to one of three groups: control (n = 28), overweight (n = 26) and obese (n = 26). Then, we measured in plasma, the levels of glucose, triacylglycerol (TAG), insulin, free fatty acids (FFAs), leptin and cytokines (e.g. interleukin-6 [IL-6] and tumor necrosis factor-alpha [TNF-alpha]) and OS biomarkers, such as lipohydroperoxides (LHP), malondialdehyde (MDA) and protein carbonylation (PC) in RBCs. We found significant positive correlations between OS biomarkers, body mass index (BMI) and pregnancy progression. Seven (26.9%) obese women who were diagnosed with GDM at 24-28 weeks of pregnancy showed significantly increased concentrations of FFAs, insulin, leptin, TNF-alpha and biomarkers of OS measured at 12-13 weeks of gestation. We propose to quantify LHP, MDA and PC in membranes of erythrocytes as possible markers to diagnose GDM from weeks 12-14.

Oxidative stress biomarkers and their relationship with cytokine concentrations in overweight/obese pregnant women and their neonates.

BACKGROUND: Oxidative damage present in obese/overweight mothers may lead to further oxidative stress conditions or inflammation in maternal and cord blood samples. Thirty-four pregnant women/newborn pairs were included in this study to assess the presence of oxidative stress biomarkers and their relationship with serum cytokine concentrations. Oxidative stress biomarkers and antioxidant enzymes were compared between the mother/offspring pairs. The presence of 27 cytokines was measured in maternal and cord blood samples. Analyses were initially performed between all mothers and newborns and later between normal weight and mothers with overweight and obesity, and diabetic/non-diabetic women. RESULTS: Significant differences were found in biomarker concentrations between mothers and newborns. Additionally, superoxide-dismutase activity was higher in pre-pregnancy overweight mothers compared to those with normal weight. Activity for this enzyme was higher in neonates born from mothers with normal pregestational weight compared with their mothers. Nitrites in overweight/obese mothers were statistically lower than in their offspring. Maternal free fatty acids, nitrites, carbonylated proteins, malondialdehyde and superoxide dismutase predicted maternal serum concentrations of IL-4, IL-13, IP-10 and MIP-1ß. Arginase activity in maternal plasma was related to decreased concentrations of IL-4 and IL-1ß in cord arterial blood. Increased maternal malondialdehyde plasma was associated with higher levels of IL-6 and IL-7 in the offspring. CONCLUSIONS: Oxidative stress biomarkers differ between mothers and offspring and can predict maternal and newborn cytokine concentrations, indicating a potential role for oxidative stress in foetal metabolic and immunologic programming. Moreover, maternal obesity and diabetes may affect maternal microenvironments, and oxidative stress related to these can have an impact on the placenta and foetal growth.

[Oxidative stress, lung function and exposure to air pollutants in Mexican schoolchildren with and without asthma]. / Estrés oxidativo, función pulmonar y exposición a contaminantes atmosféricos en escolares mexicanos con y sin asma.

OBJECTIVE.: To assess the association between the air pollutants exposure on markers of oxidative stress and lung function in schoolchildren with and without asthma from Salamanca and Leon Guanajuato, Mexico. MATERIALS AND METHODS: We realized determinations of oxidative stress biomarkers and lung function tests in 314 schoolchildren. Information of air pollutants (O3, SO2, CO, PM2.5 and PM10) were obtained from monitoring stations and multiple linear regression models were run to assess the association. RESULTS: An increase of 0.09 pmol in conjugated dienes was observed by exposure to PM10 lag 1 in asthmatics from Salamanca (p<0.05). The exposure to O3 during the same day increased the concentration of Lipohydroperoxides in 4.38 nmol in asthmatics of Salamanca, as well as in 2.31 nmol by exposure to PM10 lag 2 (p<0.05). The forced vital capacity decreased by 138 and 203 ml in children without asthma, respectively, due to exposure to carbon monoxide (p<0.05). CONCLUSIONS: Exposure to air pollutants increase oxidative stress and decreased lung function in schoolchildren, with and without asthma.

OBJETIVO: Evaluar la asociación entre la exposición a contaminantes atmosféricos y marcadores de estrés oxidativo, por un lado, y la función pulmonar, por el otro, en escolares, con y sin asma, de las ciudades de Salamanca y León, en Guanajuato, México. MATERIAL Y MÉTODOS: Se realizaron determinaciones de marcadores de estrés oxidativo y pruebas de función pulmonar en 314 escolares, y se obtuvo información sobre contaminantes atmosféricos (ozono, dióxido de azufre, monóxido de carbono y partículas menores de 2.5 µm y menores de 10 µm) de las estaciones de monitoreo correspondientes. Para evaluar la asociación se corrieron modelos de regresión lineal múltiple. RESULTADOS: Con un día de retraso a la exposición a partículas menores de 10 µm (PM10), se observó un incremento de 0.09 pmol en los dienos conjugados entre niños asmáticos de Salamanca (p<0.05). La exposición a ozono durante el mismo día incrementó la concentración de lipo-hidroperóxidos en 4.38 nmol entre asmáticos de Salamanca, así como en 2.31 nmol por la exposición a PM10 para dos días de retraso (p<0.05). La capacidad vital forzada disminuyó 138 y 203 ml en niños sin asma, respectivamente, por la exposición a monóxido de carbono (p<0.05). CONCLUSIONES: La exposición a contaminantes atmosféricos incrementa el estrés oxidativo y disminuye la función pulmonar en escolares con y sin asma.

Key Clinical Factors Predicting Adipokine and Oxidative Stress Marker Concentrations among Normal, Overweight and Obese Pregnant Women Using Artificial Neural Networks.

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.

Diabetes Mellitus and Pregnancy: An Insight into the Effects on the Epigenome.

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.

Improving Cardiovascular Risk in Postmenopausal Women with an (-)-Epicatechin-Based Nutraceutical: A Randomly Assigned, Double-Blind vs. Placebo, Proof-of-Concept Trial.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: A simple, low-cost, safe (-)-epicatechin-enriched cacao supplement product can improve the cardiovascular risk in postmenopausal women.

Ultra-Processed Food Consumption during Pregnancy and Its Association with Maternal Oxidative Stress Markers.

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.

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

(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.

Resveratrol Supplementation in Obese Pregnant Rats Improves Maternal Metabolism and Prevents Increased Placental Oxidative Stress.

Maternal obesity (MO) causes maternal and fetal oxidative stress (OS) and metabolic dysfunction. We investigated whether supplementing obese mothers with resveratrol improves maternal metabolic alterations and reduces OS in the placenta and maternal and fetal liver. From weaning through pregnancy female Wistar rats ate chow (C) or a high-fat diet (MO). One month before mating until 19 days' gestation (dG), half the rats received 20 mg resveratrol/kg/d orally (Cres and MOres). At 19dG, maternal body weight, retroperitoneal fat adipocyte size, metabolic parameters, and OS biomarkers in the placenta and liver were determined. MO mothers showed higher body weight, triglycerides and leptin serum concentrations, insulin resistance (IR), decreased small and increased large adipocytes, liver fat accumulation, and hepatic upregulation of genes related to IR and inflammatory processes. Placenta, maternal and fetal liver OS biomarkers were augmented in MO. MOres mothers showed more small and fewer large adipocytes, lower triglycerides serum concentrations, IR and liver fat accumulation, downregulation of genes related to IR and inflammatory processes, and lowered OS in mothers, placentas, and female fetal liver. Maternal resveratrol supplementation in obese rats improves maternal metabolism and reduces placental and liver OS of mothers and fetuses in a sex-dependent manner.

Effect of Oropharyngeal Administration of Colostrum in Premature Newborns ≤32 Weeks of Gestation on the Immune Response and Neonatal Morbidity: A Double-Blind Randomized Clinical Trial.

Introduction: The mother's colostrum carries immunological components, such as cytokines and immunoglobulins (Igs), derived from the maternal circulation with bacteriostatic properties. Objective: The objective of this study was to evaluate the effect of oropharyngeal administration of colostrum (OPAC) vs. placebo in the first 4 days of life in premature newborns ≤32 weeks of gestation on serum Ig concentration, neonatal morbidity, and total days of hospitalization. Hypothesis: The OPAC increases serum Igs and decreases morbidity and total days of hospitalization. Materials and Methods: A double-blind randomized controlled trial was carried out. Participants were randomly assigned to one of the two groups, namely, group 1: placebo (P) (n = 50) and group 2: colostrum (C) (n = 46). A blood sample was obtained at baseline and 7 and 28 days of life to quantify immunoglobulin G (IgG), immunoglobulin A (IgA), and IgM. Results: The C group showed an increase in serum IgA on day 28 expressed as median and [interquartile range]; C: 25 [12-35] vs. P: 11 [8-18], p < 0.001. There were no significant differences in neonatal morbidity. Newborns in the colostrum group showed the completed enteral feeding earlier (days), C: 13.9 ± 7 vs. P: 17.4 ± 8.4, p < 0.04; they reached the birth weight earlier, C: 10.9 ± 2.8 vs. P: 12.9 ± 4, p < 0.01, and had less days of hospitalization, C: 60.2 ± 33.8 vs. P: 77.2 ± 47.3, p < 0.04. Neonatal mortality was lower in the colostrum group than the placebo group 0% vs. 12%, respectively, without a statistical difference (p = 0.06). Conclusion: In premature newborns ≤32 weeks of gestation, the OPAC within 4 days after birth increases serum IgA concentration at day 28 compared to placebo. Similarly, OPAC decreased the days to complete enteral feeding and reach the birth weight and total days of hospitalization. Clinical Trial Registration: [https://clinicaltrials.gov/ct2/show/NCT03578341], identifier: [NCT03578341].

Plasma Total Antioxidant Capacity and Carbonylated Proteins Are Increased in Pregnant Women with Severe COVID-19.

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.

Effect of the Cut-Off Level for Thyroid-Stimulating Hormone on the Prevalence of Subclinical Hypothyroidism among Infertile Mexican Women.

The primary aim of this study was to compare the prevalence of subclinical hypothyroidism (SCH) using two different cut-off levels for TSH values (≥2.5 mIU/L versus ≥4.1 mIU/L). The secondary objective was to analyze the clinical-biochemical characteristics in women with and without SCH. This was a retrospective cross-sectional study. In total, 1496 Mexican women with infertility were included: Group 1, women with TSH levels ranging between 0.3 and 2.49 mIU/L, n = 886; Group 2, women with TSH between 2.5 and 4.09 mIU/L, n = 390; and Group 3, women with TSH ≥4.1 mIU/L n = 220. SCH prevalence was 40.7% (CI 95%: 38.3-43.3%) with TSH cut-off ≥ 2.5 mIU/L, and 14.7% (CI 95%: 12.7-16.5%) with TSH cut-off ≥ 4.1 mIU/L, (p = 0.0001). The prevalence of overweight was higher in Group 2 than in Groups 1 and 3. Thyroid autoimmunity, obesity and insulin resistance were higher in Group 3 than in Group 1 (p < 0.05). No other differences were observed between groups. Conclusions: The prevalence of SCH in our selected patients increased almost three times using a TSH cut-off ≥ 2.5 mIU/L compared with a TSH cut-off ≥ 4.1 mIU/L. Women with TSH ≥4.1 mIU/L compared with TSH cut-off ≤ 2.5 mIU/L more often presented with obesity, thyroid autoimmunity and insulin resistance.

Intensive Medical Nutrition Therapy Alone or with Added Metformin to Prevent Gestational Diabetes Mellitus among High-Risk Mexican Women: A Randomized Clinical Trial.

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/m2, 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 (n = 45): intensive MNT-plus metformin (850 mg twice/day) or group 2 (n = 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 n = 11 (24.4%) in the MNT plus metformin group versus n = 7 (15.5%) in the MNT without metformin group: p = 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.

Gestational Weight Gain Influences the Adipokine-Oxidative Stress Association during Pregnancy.

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.

Parameters of Oxidative Stress in Reproductive and Postmenopausal Mexican Women.

In the reproductive phase, women experience cyclic changes in the ovaries and uterus, and hormones regulate these changes. Menopause is the permanent loss of menstruation after 12 months of amenorrhea. Menopause is also linked to a decrease in estrogen production, causing an imbalance in oxidative stress. We aimed to compare the three stages of lipid peroxidation, protein oxidative damage, and total antioxidant capacity (TAC) between reproductive-aged women (RAW) and postmenopausal women (PMW) in Mexico. We carried out a cross-sectional study with 84 women from Mexico City, including 40 RAW and 44 PMW. To determine the oxidative stress of the participants, several markers of lipid damage were measured: dienes conjugates (DC), lipohydroperoxides (LHP), and malondialdehyde (MDA); exposure to protein carbonyl is indicative of oxidative modified proteins, and TAC is indicative of the antioxidant defense system. Biomarkers of oxidative stress were significantly lower in RAW vs. PMW. DC were 1.31 ± 0.65 vs. 1.7 ± 0.51 pmol DC/mg dry weight (p = 0.0032); LHP were 4.95 ± 2.20 vs. 11.30 ± 4.24 pmol LHP/mg dry weight (p < 0.0001); malondialdehyde was 20.37 ± 8.20 vs. 26.10 ± 8.71 pmol MDA/mg dry weight (p = 0.0030); exposure of protein carbonyl was 3954 ± 884 vs. 4552 ± 1445 pmol PC/mg protein (p = 0.042); and TAC was 7244 ± 1512 vs. 8099 ± 1931 pmol Trolox equivalent/mg protein (p = 0.027). PMW display significantly higher oxidative stress markers compared to RAW; likewise, PMW show a higher TAC.