Search Results (504)

Background/Objectives: Gestational Diabetes Mellitus (GDM) is a global health issue with immediate and long-term maternal–fetal complications. Current diagnostic approaches, such as the Oral Glucose Tolerance Test (OGTT), have limitations in accessibility, sensitivity, and timing. This study aimed to identify key nodes and structural interactions associated with GDM using graph theory and network analysis to improve early predictive strategies. Methods: A literature review inspired by PRISMA guidelines (2004–2025) identified 44 clinically relevant factors. A directed graph was constructed using Python (version 3.10.12), and centrality metrics (closeness, betweenness, eigenvector), k-core decomposition, and a Minimum Dominating Set (MDS) were computed. The MDS, derived using an integer linear programming model, was used to determine the smallest subset of nodes with systemic dominance across the network. Results: The MDS included 20 nodes, with seven showing a high out-degree (≥4), notably Apo A1, vitamin D, vitamin D deficiency, and sedentary lifestyle. Vitamin D exhibited 15 outgoing edges, connecting directly to protective factors like HDL and inversely to risk factors such as smoking and obesity. Sedentary behavior also showed high structural influence. Closeness centrality highlighted triglycerides, insulin resistance, uric acid, fasting plasma glucose, and HDL as nodes with strong predictive potential, based on their high closeness and multiple incoming connections. Conclusions: Vitamin D and sedentary behavior emerged as structurally dominant nodes in the GDM network. Alongside metabolically relevant nodes with high closeness centrality, these findings support the utility of graph-based network analysis for early detection and targeted clinical interventions in maternal health. Full article

Background: The human fetal adrenal gland is a unique endocrine organ with distinct morphology and functional dynamics, which is significantly different from the postnatal adrenal. Its rapid growth and vital steroidogenic role during gestation have positioned it as a key regulator of fetal development and pregnancy maintenance. Objectives: To provide a comprehensive overview of the morphogenesis, function, regulatory mechanisms, and clinical implications of the human fetal adrenal gland, highlighting recent advances in understanding its development and its role in prenatal and postnatal health outcomes. Methods: A systematic review was conducted, including original research articles focused on human fetuses or validated animal models, examining the genetic, molecular, and hormonal mechanisms underlying adrenal development and function. Studies were excluded if they were editorials, case reports, focused on adult adrenal physiology, had small sample sizes, or were non-English publications. Study quality was evaluated using PRISMA guidelines. Results: The fetal adrenal gland develops from both mesodermal and ectodermal origins, forming three primary zones: fetal, transitional, and definitive. Each zone has distinct functions and developmental pathways. The fetal zone, which predominates, is responsible for producing dehydroepiandrosterone sulfate, DHEA-S, which is crucial for placental estrogen synthesis. The adrenal gland undergoes rapid growth and functional maturation, regulated by ACTH, placental CRH, IGF, and the renin–angiotensin system. Disruption of adrenal function is associated with conditions such as preterm birth, adrenal hypoplasia, congenital adrenal hyperplasia, and intrauterine growth restriction. Emerging evidence suggests that fetal adrenal hormones may influence long-term health through fetal programming mechanisms. Conclusions: The fetal adrenal gland plays a critical and multifaceted role in fetal and placental development. This gland influences placental development via steroid precursors (DHEA-S → estrogen synthesis), while also being regulated by placental factors such as the corticotropin-releasing hormone. Understanding its complex structure–function relationships and regulatory networks is essential for predicting and managing prenatal and postnatal pathologies. Future research should focus on elucidating molecular mechanisms, improving diagnostic tools, and exploring long-term outcomes of altered fetal adrenal function. Full article

Environmental stressors during the crucial period of fetal development can have a substantial impact on long-term health outcomes. A major concern is dietary exposure to endocrine-disrupting chemicals (EDCs), which can readily cross the placenta and disrupt fetal hormonal signaling and developmental programming. Examples of these chemicals include bisphenols, phthalates, pesticides, and persistent organic pollutants (POPs). Prenatal exposure to EDC has been associated with long-term effects in children, including immune disruption, metabolic dysregulation, impaired neurodevelopment, and reproductive alterations, as evidenced by human cohort studies and experimental models. Epigenetic reprogramming, direct interference with endocrine signaling, and oxidative stress (OS) are hypothesized pathways for these adverse consequences, which often combine to produce long-lasting physiological changes. This narrative review summarizes current research on maternal dietary exposure to EDCs during pregnancy, highlighting associations with adverse child health outcomes. It also discusses the growing evidence of transgenerational effects, the potential mechanisms linking prenatal exposure to long-term outcomes, and the importance of understanding the roles of timing, dosage, and chemical type. By highlighting the necessity of focused interventions to lower maternal EDC exposure and lessen threats to the health of offspring, the review concludes by discussing implications for future research, preventive measures, and public health policy. Full article

Caffeine is one of the most widely consumed psychoactive substances globally and is a common component of daily diets, particularly among women of reproductive age. Numerous in vitro and in vivo studies have indicated potential adverse effects of prenatal caffeine exposure, including disturbances in fetal growth, metabolic dysregulation, organ malformations, and neurodevelopmental alterations. These findings suggest that caffeine may influence multiple physiological pathways during gestation, including epigenetic modifications and metabolic programming. However, evidence from human studies remains heterogeneous and often inconclusive. Recent cohort studies and meta-analyses have reported that moderate maternal caffeine intake is not significantly associated with increased risks of gestational diabetes mellitus, gestational hypertension, or preeclampsia, although higher intake levels have been linked to anemia, preterm birth, and low birth weight in some populations. Furthermore, emerging data suggest potential associations between prenatal caffeine exposure and early neurodevelopmental outcomes, including behavioral changes, subtle structural brain differences, and alterations in offspring metabolic health and obesity risk. Despite these findings, the magnitude and clinical relevance of these effects remain uncertain, partly due to variability in caffeine sources, dosages, study designs, and reliance on self-reported intake. This review aims to synthesize current evidence on maternal caffeine consumption, its impact on pregnancy complications, fetal development, and long-term child health outcomes. By integrating experimental and clinical data, the study provides a comprehensive overview that may assist clinicians and healthcare professionals in counseling pregnant women regarding caffeine intake and potential risks. Full article

Background/Objectives: Gestational weight gain (GWG) is a crucial factor influencing mother and fetal health, as high GWG is associated with adverse pregnancy outcomes and an increased long-term risk of obesity and metabolic issues in the children. In addition to controlling weight, maternal physical activity (PA) during pregnancy may influence fetal development through potential epigenetic mechanisms, including histone modifications, DNA methylation, and the production of non-coding RNA. Methods: This narrative review synthesizes evidence from randomized controlled trials (RCTs; n = 11, 3654 participants) investigating the impact of aerobic PA on GWG, while also highlighting emerging, primarily indirect findings on maternal–fetal epigenetic programming. Results: The majority of RCTs found that supervised PA interventions, especially when paired with nutritional counseling, decreased both the incidence of excessive GWG and total GWG. Enhancements in lipid metabolism, adipokine profiles, and maternal insulin sensitivity point to likely biochemical mechanisms that connect PA to epigenetic modification of fetal metabolic genes (e.g., IGF2, PGC-1α, LEP). Animal and observational studies suggest that maternal activity may influence offspring epigenetic pathways related to obesity and cardiometabolic conditions, although direct human evidence is limited. Conclusions: In addition to potentially changing gene–environment interactions throughout generations, prenatal PA is a low-cost, safe method of improving maternal and newborn health. Future RCTs ought to incorporate molecular endpoints to elucidate the epigenetic processes by which maternal exercise may provide long-term health benefits. Full article

Prenatal maternal stress (PNMS) predicts risk for autism spectrum disorders (ASD), although the mechanisms are unknown. Because ASD and autistic-like traits have been associated with both prenatal stress and DNA methylation differences, it is important to examine whether epigenetic mechanisms mediate the pathway from PNMS to later autistic-like outcomes. This study aimed to determine the extent to which DNA methylation mediates the association between PNMS from a natural disaster and autistic-like traits in offspring assessed during adolescence. Five months following the 1998 ice storm in Quebec, we recruited women who had been pregnant during the crisis and assessed their PNMS: objective hardship, subjective distress, and cognitive appraisal. At age 13, their children provided blood samples for DNA. At ages 15, 16 and 19, the youth self-reported their own autistic-like traits using the Broad Autism Phenotype Questionnaire. This longitudinal design allowed us to track the developmental pathway from prenatal exposure, through adolescent DNA methylation, to later behavioral outcomes. Analyses included youth with data on PNMS, DNA methylation, and the BAPQ (n = 27 at age 15; 22 at age 16; and 13 at age 19). Results showed that mothers’ disaster-related objective hardship and their negative cognitive appraisal of the disaster were associated with DNA methylation at age 13, which then were associated with the severity of their children’s Aloof Personality and Pragmatic Language Deficits, but not Rigid Personality, at ages 15, 16 and 19. Mediation was significant particularly through genes within the PI3K/AKT/mTOR pathway, which has been implicated in various neurodevelopmental disorders, including ASD. Interestingly, while greater PNMS predicted more severe ASD traits, the epigenetics effects were for less severe traits. Although other interpretations are possible, these results could suggest that DNA methylation, assessed in early adolescence, may protect against ASD traits at later ages, particularly when there is a mismatch between the prenatal environment (disaster) and the postnatal environment (absence of disaster). The interpretation of these findings benefits from the longitudinal design and is discussed in the context of fetal programming and the predictive adaptive response. Full article

Background/Objectives: In Brazil, nearly universal access to prenatal care coexists with ongoing negative fetal and infant outcomes. This review explores how the adequacy of prenatal care affects maternal, fetal, and child health, and highlights recurring gaps in service delivery. Methods: A narrative review of Brazilian studies published between 2018 and 2024 was conducted through the Virtual Health Library and PubMed. The initial search (July 2024) was updated in February 2025, and two reviewers independently screened and extracted data, synthesizing clinical outcomes from the findings. Results: A total of thirty-six studies were included in the review. Inadequate prenatal care was consistently linked to higher rates of infant and neonatal mortality, prematurity, low birth weight, congenital syphilis, and neonatal near misses. The studies indicated that counting visits alone does not adequately reflect the quality of care: when evaluated against the Prenatal and Birth Humanization Program (PHPN), most studies met only one of the eight minimum criteria. Common shortcomings included late initiation of care, incomplete diagnostic testing, fragmented follow-up, and insufficient treatment for partners regarding sexually transmitted infections. Conclusions: Adverse outcomes persist in Brazil not due to a lack of access, but rather due to deficiencies in the content and continuity of prenatal care. To improve perinatal outcomes, it is essential to strengthen care through standardized, multidimensional indicators and integrated strategies that combine clinical, educational, and psychosocial support. Full article

Background and objectives: Hypertension is a worldwide burden, for which fetal malnutrition is a risk factor. Another societal challenge is environmental waste. Our research focusses on cocoa shell extract (CSE), a cocoa by-product with antioxidant bioactive components. Male rats exposed to fetal malnutrition develop hypertension and endothelial dysfunction, which are improved by CSE supplementation. We hypothesized that effects of CSE are related to an antioxidant action. Methods: Adult male and female offspring of dams exposed to 50% food restriction during gestation (MUN) and controls were supplemented for 3 weeks with CSE (250 mg/kg/day) or a vehicle. We assessed plasma SOD activity, GSH and carbonyls (via spectrophotometry) and aortic expression of enzymes related to ROS degradation or production (via Western blotting). Results: MUN males showed lower Nrf2 expression and increased carbonyls, SOD activity and mitochondrial SOD2 expression, without alterations in GSH or the related enzyme CGLM. No changes in xanthine oxidase or NADPH subunits (p22phox and p47phox) were detected, suggesting a different origin of superoxide anion. Phosphorylated-eNOS/eNOS and 3-nitrotyrosine expression were increased without changes in plasma nitrates. MUN females only showed plasma SOD and aortic 3-nitrotyrosine elevation. CSE supplementation reduced SOD2 and p-eNOS/eNOS expression and SOD activity and increased Nrf2 expression. Conclusions: MUN arteries exhibit oxidative damage, with a higher impact on males. SOD2 and p-eNOS/e-NOS overexpression may be a counteracting mechanism that compensates for superoxide anion overproduction, likely involving mitochondria. The reversal of these alterations by CSE supplementation is probably related to a reduction in vascular superoxide anion through a direct scavenging action of its bioactive components. A longer supplementation period may be needed to increase endogenous antioxidants through Nrf2 and to reduce oxidative–nitrosative damage. Full article

Background: Mitochondria are essential for fetal development, regulating energy metabolism and metabolic programming. This study examined how maternal nutrition and one-carbon metabolite (OCM) supplementation during early gestation affect mitochondrial function in fetal liver and muscle at day 161 of gestation in beef heifers. Methods: Twenty-nine crossbred Angus heifers were assigned to one of four treatments in a 2 × 2 factorial design: control (CON; 0.45 kg/day ADG) or restricted gain (RES; −0.23 kg/day), with or without OCM supplementation. Treatments were applied from breeding to day 63 of gestation, after which all heifers received a common diet. Fetal liver and muscle tissues were collected at day 161. Mitochondrial respiration (Seahorse assay), mtDNA copy number (qPCR), and mitochondria-related gene expression (RNA-seq) were assessed. Results: In fetal liver, state 3 respiration was highest in CON + OCM, while state 4o respiration was lowest in RES + OCM (p ≤ 0.05). mtDNA copy number was greater in RES and +OCM groups. In fetal muscle, mtDNA copy number was influenced by gain, but respiration was unaffected. Transcriptomic analysis revealed more mitochondria-related differentially expressed genes (mtDEGs) in fetal muscle than liver (90% versus 10% of total mtDEG), with most genes downregulated in the RES and +OCM groups compared to the CON and −OCM groups (FDR ≤ 0.10). Conclusions: OCM supplementation enhanced mitochondrial respiration and biogenesis in fetal liver, likely via post-translational mechanisms. In contrast, fetal muscle showed downregulation of mitochondria-related genes without functional changes, indicating transcriptional reprogramming with potential effects on later metabolic function. These results underscore early gestation as a critical window for OCM-based nutritional interventions to improve metabolic outcomes in livestock. Full article

Background: Abiogenesis is hypothesized to have occurred in the aquatic environments of the early Earth approximately 3.8–4.0 billion years ago, in oceans containing high concentrations of ions (Na⁺ ≈ 470 mmol/L, Cl⁻ ≈ 545 mmol/L, Mg²⁺ ≈ 51–53 mmol/L, Ca²⁺ ≈ 10 mmol/L, K⁺ ≈ 10 mmol/L, SO₄²⁻ ≈ 28–54 mmol/L, HCO₃⁻ ≈ 2.3 mmol/L). Primitive membranes evolved ion-regulatory mechanisms to sustain electrochemical gradients, enabling metabolic activity. Objectives: This review compares the composition of amniotic fluid (AF) to seawater, framing AF as a “biological ocean” for the fetus, and evaluates the impact of micro- and nanoplastics (MNPs) on this protected milieu. Methods: We synthesized data from published studies on concentrations of and ions and other important substances in AF during pregnancy and compared them with marine values. Reports of MNPs detected in placenta, AF, and human organs were systematically reviewed. Results: AF exhibits high ionic similarity to seawater, although the absolute concentrations of ions are lower, reflecting evolutionary conservation. Recent analytical studies identified MNPs in samples of human placenta (4–10 particles per 1 g of tissue), meconium (median 3–5 particles per g), and AF (detectable in >60% of tested samples). Co-exposure to heavy metals, persistent organic pollutants, and endocrine disruptors were reported in 20–40% of maternal–fetal samples. Conclusions: The analogy between oceans and AF underscores a conserved evolutionary continuum. However, the infiltration of MNPs into intrauterine environments is a novel toxicological challenge with potential implications for neurodevelopment, immune programming, and epigenetic regulation. Within the One Health framework, protecting AF from anthropogenic contaminants is as critical as safeguarding marine ecosystems. Full article

Prenatal alcohol exposure (PAE) causes neurobehavioral deficits and metabolic syndrome in later life. Prenatal choline supplementation (PCS) improves those behavioral deficits. Here we test whether PCS also ameliorates the attendant metabolic syndrome, using an established mouse model that mirrors aspects of alcohol-related neurodevelopmental disorders. Pregnant dams were exposed to alcohol (3 g/kg) from gestational days 8.5–17.5; some dams received additional choline (175% of requirement) by a daily injection. Offspring were followed through to the age of 86 wks with respect to their body composition and glucose tolerance. We found that PAE affected these outcomes in a sex-dependent manner. Male PAE offspring exhibited an increased fat mass, liver enlargement, elevated fasting glucose, and glucose intolerance. Female PAE offspring exhibited an increased fat mass, but the glucose tolerance and fasting values were unaffected. Regardless of sex, PCS attenuated all these metabolic measures. PCS was shown previously to elevate methyl-related choline metabolites and improve fetal growth, suggesting that it acts by attenuating the in utero stressors that otherwise program the fetus for metabolic syndrome in later life. Importantly, PCS also improved the adiposity, fasting glucose, and glucose tolerance in control offspring consuming the fixed-nutrient AIN-93G diet, suggesting that its choline content (1 g/kg) may be inadequate for optimal rodent health. Full article

We investigated gene regulatory relationships in the neonatal liver to identify potential mechanisms by which maternal vitamin and mineral supplementation during gestation influences developmental programming in heifer calves. Liver transcriptomes were profiled by RNA-Seq in calves collected 30 h after birth from dams fed either a basal diet (CON; n = 6) or the basal diet plus a vitamin and mineral premix (VTM; n = 6; 113 g·heifer⁻¹·d⁻¹), starting 60 days pre-breeding and continuing through gestation. Using DESeq2, we identified 630 DEGs between treatment groups (p ≤ 0.05 and |log2FC| ≥ 0.5). Over-represented pathways included oxidative phosphorylation, AMPK, PI3K/Akt, and FoxO, key regulators of energy homeostasis. We also identified 58 transcription factors (TFs) and 435 differentially connected genes (p ≤ 0.05), suggesting maternal diet induced a regulatory rewiring of TFs and histone deacetylating genes. Gene set enrichment analysis revealed genes positively ranked, such as LRAT and LMBRD1, underlying the vitamin digestion and absorption pathway, indicating coordinated upregulation in the VTM group. Conversely, 23 DEGs associated with the OXPHOS KEGG pathway were downregulated in the VTM calves. Further research should explore whether these transcriptional changes are linked to epigenetic modifications established at birth, persist throughout postnatal development, and potentially contribute to multigenerational inheritance. Full article

The impact of maternal dietary restriction and hydroxytyrosol (HT) supplementation during the last third of gestation on plasma malondialdehyde (MDA) concentration, total antioxidant capacity (ABTS assay), and peripheral blood gene expression related to antioxidant defence, immune response, and energy metabolism was evaluated in beef cows and calves. Two feeding treatments in late gestation (T100% vs. T60% of nutrient requirements) and two HT levels (Control vs. HT at 180 mg/kg of diet) were evaluated during gestation (n = 46 cows) and lactation (n = 37 cows and calves). In pregnant cows, undernutrition led to inhibition of glucose oxidation (PDK4), decreased lipid synthesis (HMGCS1 and SCD) and TLR signalling; T60% cows showed higher plasma MDA (p < 0.05) with no positive effect of HT on antioxidant capacity. Contrarily, during lactation, earlier HT supplementation upregulated antioxidant capacity and modulated antioxidant gene expression (p < 0.05). In calves, there was an increase in SOD1, CAT, and GPX1, especially in the T60%-HT group (p < 0.05). Interestingly, HT supplementation increased glucose transport (SLC2A1/GLUT1) during pregnancy and lactation (p < 0.05). However, it caused different effects on immunometabolic regulation in both dams and calves, depending on maternal diet. Overall, maternal HT supplementation under restricted nutritional conditions promoted postpartum antioxidant capacity and modulated immune and metabolic gene expression in cows and calves. Full article

Prenatal exposure to air pollution is a major public health concern due to its potential to impair fetal brain development. This study examined whether maternal inflammatory and oxidative stress biomarkers mediate the association between trimester-specific air pollutant exposure during pregnancy and infant neurodevelopment at one year. We analyzed 87 mother–infant pairs from the OBESO perinatal cohort in Mexico City. Trimester-specific exposure to CO, PM₁₀, PM_2.5, SO₂, and O₃ was estimated using residential geolocation. Biomarkers were measured in the first and third trimesters by protocol, and intra-pregnancy change was calculated as Δ(3T–1T) for cytokines (IL-1β, IL-6, TNFα) and oxidative stress markers (malondialdehyde (MDA), protein carbonyls (PC), and total antioxidant capacity (TAC). Infant neurodevelopment at 12 months was assessed using Bayley-III. Exploratory mediation analyses were conducted, adjusting for gestational age at birth, pre-eclampsia, gestational diabetes, fetal growth restriction, marital status, mode of delivery, and infant sex; bootstrapping was applied to obtain robust estimates. Third-trimester CO exposure was associated with poorer receptive language (coef = 0.754, p = 0.02). PM_2.5 exposure showed direct effects on expressive language in the first (coef = 0.01, p = 0.04) and third trimesters (coef = 0.007, p = 0.015) in models including IL-1β. Third-trimester O₃ and SO₂ exposures were linked to lower expressive scores in models including TNFα (coef = 0.007, p = 0.02), MDA (coef = 0.008, p = 0.04), and PC (coef = 0.007, 95% p = 0.04). Meanwhile PM₁₀ exposure was associated with socio-emotional outcomes in models with IL-6 and TAC (coef = 0.003, p = 0.04). These findings indicate that maternal inflammation and oxidative stress biomarkers did not mediate the associations between prenatal air pollution exposure and infant neurodevelopment, and this study cannot elucidate their specific biological role in neurodevelopment. Full article