Search Results (394)

Maternal undernutrition (MUN) causes severe metabolic disruption in the offspring of mammals. Here we determined the role of histone modification in hepatic gene expression in late-gestation fetuses of nutritionally restricted cows, an established model using low-nutrition (LN) and high-nutrition (HN) conditions. The chromatin immunoprecipitation sequencing results show that genes with an altered trimethylation of histone 3 lysine 4 (H3K4me3) are associated with cortisol synthesis and secretion, the PPAR signaling pathway, and aldosterone synthesis and secretion. Genes with the H3K27me3 alteration were associated with glutamatergic synapse and gastric acid secretion. Compared to HN fetuses, promoter H3K4me3 levels in LN fetuses were higher in GDF15, IRF2BP2, PPP1R3B, and QRFPR but lower in ANGPTL4 and APOA5. Intriguingly, genes with the greatest expression changes (>1.5-fold) exhibited the anticipated up-/downregulation from elevated or reduced H3K4me3 levels; however, a significant relationship was not observed between promoter CpG methylation or H3K27me3 and the gene set with the greatest expression changes. Furthermore, the stress response genes EIF2A, ATF4, DDIT3, and TRIB3 were upregulated in the MUN fetal liver, suggesting activation by upregulated GDF15. Thus, H3K4me3 likely plays a crucial role in MUN-induced physiological adaptation, altering the hepatic gene expression responsible for the integrated stress response and systemic energy metabolism, especially circulating lipoprotein lipase regulation. Full article

Gestational diabetes mellitus (GDM) and iron deficiency anemia (IDA) are the most common pregnancy-related conditions resulting in adverse maternal and fetal complications. MicroRNAs (miRNAs), particularly miR-182-3p and miR-24-3p, are promising biomarkers as they act as regulatory elements in various diseases; however, their roles in GDM and IDA are unclear. The present study aimed to analyze the expression and functional relevance of miR-182-3p and miR-24-3p in GDM and IDA. Experimental validation via RT-PCR revealed significant upregulation of both miRNAs in GDM and IDA samples. We identified common target genes and signaling pathways associated with these miRNAs, using a combination of data mining, bioinformatic tools (miRDB, TargetScan, miRTarBase, and miRWalk), and differentially expressed gene (DEGs) analysis using the GEO, OMIM, MalaCards, and GeneCards datasets. GO and KEGG pathway analyses revealed that the shared miRNA–mRNA in target genes were enriched in insulin signaling, apoptosis, and inflammatory pathways—key mechanisms implicated in GDM and IDA. Furthermore, hub genes such as IRS1, PIK3CA, CASP3, MAPK7, and PDGFRB were identified, supporting their central role in metabolic dysregulation during pregnancy. These findings demonstrate the potential of miR-182-3p and miR-24-3p as diagnostic biomarkers and therapeutic targets in managing GDM and IDA, offering new insights into the molecular interplay underlying pregnancy complications. Full article

Background: Taste changes are common during pregnancy and can have a significant impact on dietary habits. Objective: This study aimed to investigate the influence of the perception of sweet and fat taste on diet in pregnant diabetic women. Methods: This cross-sectional observational study included 66 pregnant women, 33 with gestational diabetes and 33 with pre-gestational type 2 diabetes. Taste perception tests were conducted to evaluate thresholds for detecting sweet and fatty tastes. Dietary surveys were used to assess daily nutrient intake, and various biochemical parameters, such as glycemia, HbA1c, and cholesterol, were analyzed. Results: The low-fat taster group (threshold > 0.75 mmol/L) included more patients with diabetes compared to those with gestational diabetes. All diabetic patients had low sucrose perception. Although pregnant women with gestational diabetes detected sweetness at high concentrations, pregnant women with diabetes detected it at lower concentrations (0.012 ± 0.023 mmol/L vs. 0.006 ± 0.005 mmol/L; p = 0.3). High-fat tasters exhibited elevated glycemia compared to low-fat tasters (6.04 ± 1.88 mmol/L vs. 7.47 ± 3.4 mmol/L; p = 0.03). They also had higher cholesterol (p = 0.04) and lower HDL-C levels (4.96 ± 1.04 mmol/L vs. 1.36 ± 0.29 mmol/L; p = 0.03). High-fat tasters showed more frequent daily consumption of oil, butter, cheese, and chocolate. The highly sweet tasters had higher cholesterol levels and lower LDL levels. Individuals who reported being highly sensitive to sweet taste consumed more daily oil, sweetened yogurt, or cream desserts, as well as white sugar. Conclusions: These findings indicate that altered sensitivity to fat and sweet tastes is associated with different dietary habits and metabolic profiles in pregnant women with diabetes. Specifically, reduced sensitivity to the taste of fat is associated with higher consumption of high-fat foods and poorer lipid profiles. In contrast, sensitivity to sweet taste correlates with an increased intake of sugary and fatty foods. Understanding these taste-related behaviors can help develop personalized nutritional strategies to improve metabolic control and maternal–fetal outcomes in this high-risk group. Full article

Childhood obesity is a growing global health concern, with established links to physical activity, nutrition, and, increasingly, to prenatal and perinatal factors. Emerging evidence highlights the significant role of maternal conditions such as obesity, comorbidities, nutrition, and environmental exposures in predisposing offspring to long-term metabolic and cardiovascular diseases. The “Developmental Origins of Health and Disease” (DOHaD) paradigm provides a framework for understanding how early life environmental exposures, particularly during the periconceptional, fetal, and neonatal periods, can program future health outcomes through epigenetic mechanisms. Epigenetic modifications alter gene expression without changing the DNA sequence and are increasingly recognized as key mediators in the development of obesity. This narrative review summarizes current findings on the early determinants of childhood obesity, emphasizing the molecular and epigenetic pathways involved. A comprehensive literature search was conducted across multiple databases and international sources, focusing on recent studies from the past decade. Both human and animal research were included to provide a broad perspective. This review aims to consolidate recent insights into early life influences on obesity, underscoring the need for preventive strategies starting as early as the preconception period. Full article

Preeclampsia (PE) is a multifactorial hypertensive disorder unique to pregnancy and a leading cause of maternal and fetal morbidity and mortality worldwide. Its pathogenesis involves placental dysfunction and an exaggerated maternal inflammatory response. Uric acid (UA), traditionally regarded as a marker of renal impairment, is increasingly recognized as an active contributor to the development of PE. Elevated UA levels are associated with oxidative stress, endothelial dysfunction, immune activation, and reduced renal clearance. Clinically, UA is measured in the second and third trimesters to assess disease severity and guide obstetric management, with higher levels correlating with early-onset PE and adverse perinatal outcomes. Its predictive accuracy improves when combined with other clinical and biochemical markers, particularly in low-resource settings. Mechanistically, UA and its monosodium urate crystals can activate the NLRP3 inflammasome, a cytosolic multiprotein complex of the innate immune system. This activation promotes the release of IL-1β and IL-18, exacerbating placental, vascular, and renal inflammation. NLRP3 inflammasome activation has been documented in placental tissues, immune cells, and kidneys of women with PE and is associated with hypertension, proteinuria, and endothelial injury. Experimental studies indicate that targeting UA metabolism or inhibiting NLRP3 activation, using agents such as allopurinol, metformin, or MCC950, can mitigate the clinical and histopathological features of PE. These findings support the dual role of UA as both a biomarker and a potential therapeutic target in the management of the disease. Full article

The maternal–fetal environment is influenced by multiple factors, including nutrition and environmental contaminants, which can impact long-term development. Perinatal exposure to organophosphate flame retardants (OPFRs) disrupts energy homeostasis and causes maladaptive behaviors in mice. Maternal obesity affects development by impairing blood–brain barrier (BBB) formation, influencing brain regions involved in energy regulation and behavior. This study examined the combined effects of maternal obesity and perinatal OPFR treatment on offspring development. Female mice were fed either a low-fat (LFD) or a high-fat diet (HFD) for 8 weeks, mated, and treated with either sesame oil or an OPFR mixture (tris(1,3-dichloro-2-propyl)phosphate, tricresyl phosphate, and triphenyl phosphate, 1 mg/kg each) from gestational day 7 to postnatal day 14. Results showed that both maternal diet and OPFR treatment disrupted blood–brain barrier integrity, energy balance, and reproductive gene expression in the hypothalamus of neonates. The expression of hepatic genes related to lipid and xenobiotic metabolism was also altered. In adulthood, LFD OPFR-treated female offspring exhibited increased avoidance behavior, while HFD OPFR-treated females demonstrated memory impairments. Metabolic assessments revealed decreased energy expenditure and nighttime activity in LFD OPFR-treated females. These findings suggest that maternal diet and OPFR treatment alter hypothalamic and liver gene expression in neonates, potentially leading to long-term metabolic and behavioral changes. Full article

Background/Objectives: Gestational diabetes (GD), which affects approximately 15% of pregnancies worldwide, poses significant risks to both maternal and fetal health, underscoring the need for effective prevention and management strategies. This umbrella review aims to evaluate the role of probiotics in the prevention of GD. Methods: The review was conducted in accordance with the Joanna Briggs Institute (JBI) Manual for Evidence Synthesis. A comprehensive literature search was performed in November 2024 across four databases: PubMed/Medline, Cochrane Library, Embase, and CINAHL. A total of 307 articles were identified, of which 6 met the inclusion criteria and were included in the final synthesis. Results: Probiotic supplementation was associated with a significant reduction in the incidence of GD in selected populations, particularly in women with a body mass index (BMI) < 26, age < 30 years [Relative Risk (RR): 0.58], and p < 0.05 in the other studies included, alongside improvements in several metabolic parameters. However, consistent benefits on maternal or neonatal complications were not observed but a 33% reduction in GD was confirmed (RR 0.67). The combination of probiotics with healthy lifestyle behaviors appeared to exert a stronger protective effect against GD and its potential complications. Conclusions: This umbrella review suggests that probiotics—particularly multi-strain formulations—may have a potential role in reducing the risk of GD in certain populations. However, the findings across the included studies are inconsistent and sometimes conflicting. While probiotics are generally considered safe and have recognized benefits for metabolic health, their efficacy as an adjunct intervention for GD prevention remains not fully clear. Further well-designed research is needed to clarify which specific probiotic interventions may be effective and to better guide clinical practice. Full article

Obesity affects approximately 30% of pregnancies worldwide and is one of the leading metabolic disorders among pregnant women. Maternal obesity is often associated with placental dysfunction and structural alterations, which increase the risk of developing complications. Efflux transporters, including P-glycoprotein (P-gp), may impact placental function and fetal development. Consequently, our research examined the effects of obesity on P-glycoprotein expression in both a rat model and human placental tissue. P-gp expression was measured by RT-PCR and Western blot techniques in human and rat placental tissues. Moreover, we further characterized the high-fat and high-sugar diet (HFHSD)-induced gestational obesity rat model by measuring tissue weights. Significant decreases were observed in fetal, placental, and uterus weights in the obese animals near the end of pregnancy. In obese rats, mRNA and protein expression of placental P-gp showed a reduction on gestation days 15, 20, and 22. A similar P-gp reduction was observed in the term placenta in obese women in mRNA and protein levels. We hypothesize that the reduced expression of P-gp may heighten the susceptibility of both the fetus and placenta to P-gp substrates. This alteration could potentially result in an increased risk of pregnancy complications and obesity-related drug contraindications linked to P-gp transport during pregnancy. Full article

Preeclampsia (PE) is a pregnancy-specific hypertensive disorder characterized by systemic inflammation, endothelial dysfunction, and placental insufficiency. While inadequate trophoblast invasion and impaired spiral artery remodeling have long been recognized as central to its pathogenesis, emerging evidence underscores the critical roles of dysregulated iron metabolism and its crosstalk with immune responses, particularly macrophage-mediated inflammation, in driving PE development. This review systematically explores the dynamic changes in iron metabolism during pregnancy, including increased maternal iron demand, placental iron transport mechanisms, and the molecular regulation of placental iron homeostasis. We further explore the contribution of ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, to trophoblast dysfunction and pregnancy-related diseases, including PE. Macrophages, pivotal immune regulators at the maternal–fetal interface, exhibit distinct polarization states that shape tissue remodeling and immune tolerance. We outline their origin, distribution, and polarization in pregnancy, and emphasize their aberrant phenotype and function in PE. The bidirectional crosstalk between iron and macrophages is also dissected: iron shapes macrophage polarization and function, while macrophages reciprocally modulate iron homeostasis. Notably, excessive reactive oxygen species (ROS) and pro-inflammatory cytokines secreted by M1-polarized macrophages may exacerbate trophoblast ferroptosis, amplifying placental injury. Within the context of PE, we delineate how iron overload and macrophage dysfunction synergize to potentiate placental inflammation and oxidative stress. Key iron-responsive immune pathways, such as the HO-1/hepcidin axis and IL-6/TNF-α signaling, are discussed in relation to disease severity. Finally, we highlight promising therapeutic strategies targeting the iron–immune axis, encompassing three key modalities—iron chelation therapy, precision immunomodulation, and metabolic reprogramming interventions—which may offer novel avenues for PE prevention and treatment. Full article

The thyroid gland plays a crucial role in regulating metabolism and supporting development through the production of the hormones T4 and T3. These hormones are essential during childhood for nervous system myelination, physical growth, puberty, skeletal and dental maturation, and overall metabolic balance. In early infancy, when the hypothalamic–pituitary–thyroid axis is still immature, thyroid dysfunction can result in a range of long-term complications. The metabolism and action of thyroid hormones depend not only on iodine but also on other vital micronutrients, particularly selenium (Se). This narrative review aims to comprehensively examine the role of selenium in maintaining thyroid health from fetal life through adolescence. Selenium is a key micronutrient involved in thyroid development, hormone synthesis, antioxidant defense, and immune regulation, especially during pregnancy and childhood. Inadequate selenium levels may contribute to the onset, progression, and clinical management of various thyroid disorders, particularly hypothyroidism and autoimmune thyroid diseases. Although scientific evidence supports selenium’s critical functions in hormone metabolism and antioxidant protection, public awareness and monitoring of selenium intake remain insufficient. Beyond the need for further research, there is an urgent call for integrated public health strategies, ranging from sustainable, food-based approaches to targeted clinical screening and educational programs. Promoting awareness of selenium’s importance and incorporating selenium status into maternal and pediatric care protocols could play a significant role in preventing deficiencies and supporting long-term endocrine and neurodevelopmental health. Full article

Maternal obesity programs the fetus for increased risk of chronic disease development in early life and adulthood. We hypothesized that maternal nutrient excess leads to fetal inflammation and impairs offspring skeletal muscle mitochondrial biogenesis in non-human primates. At least 12 months before pregnancy, female baboons were fed a normal chow (CTR, 12% energy fat) or a maternal nutrient excess (MNE, 45% energy fat, and ad libitum fructose sodas) diet, with the latter to induce obesity. After 165 days of gestation (0.9 G), offspring baboons were delivered by cesarean section, and the soleus muscle was collected (CTR n = 16, MNE n = 5). At conception, MNE mothers presented increased body fat and weighed more than controls. The soleus muscle of MNE fetuses exhibited increased levels of stress signaling associated with inflammation (TLR4, TNFα, NF-kB p65, and p38), concomitant with reduced expression of key regulators of mitochondrial biogenesis, including PGC1α, both at the protein and transcript levels, as well as downregulation of PPARGC1B, PPARA, PPARB, CREB1, NOS3, SIRT1, SIRT3. Decreased transcript levels of NRF1 were observed alongside diminished mitochondrial DNA copy number, mitochondrial fusion elements (MFN1, MFN2), cytochrome C protein levels, and cytochrome C oxidase subunits I and II transcripts (cox1 and cox2). MNE coupled to MO-induced stress signaling in fetal baboon soleus muscle is associated with impaired mitochondrial biogenesis and lower mitochondrial content, resembling the changes observed in metabolic dysfunctions, such as diabetes. The observed fetal alterations may have important implications for postnatal development and metabolism, potentially increasing the risk of early-onset metabolic disorders and other non-communicable diseases. Full article

Background/Objectives: Gestational diabetes mellitus (GDM) is a common metabolic disorder during pregnancy, associated with increased risks for both maternal and fetal complications. Insulin resistance plays a central role in its pathophysiology. This study aimed to evaluate the predictive value of the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) in diagnosing GDM and to explore its correlation with clinical and anthropometric parameters in a Romanian population. Methods: A retrospective case–control study was conducted on 320 pregnant women between 24 and 28 weeks of gestation. Based on ADA criteria, participants were divided into 160 with GDM and 160 controls, matched by age and gestational week. Fasting glucose, insulin, BMI, and blood pressure were assessed. HOMA-IR and HOMA-β were calculated. Statistical analyses included t-tests, Pearson correlation, and logistic regression. Results: HOMA-IR was significantly higher in the GDM group (2.9 vs. 1.8; p < 0.001). It correlated with fasting insulin (r = 0.85, p < 0.001), fasting glucose (r = 0.65, p < 0.001), BMI (r = 0.60, p < 0.001), and systolic blood pressure (r = 0.42, p < 0.001). Logistic regression identified HOMA-IR as an independent predictor of GDM (OR = 2.4, 95% CI: 1.6–3.5, p < 0.001), along with BMI (p = 0.01) and maternal age (p = 0.05). Conclusions: HOMA-IR is significantly associated with GDM and may enhance mid-gestational risk assessment when combined with clinical and anthropometric measures. Further studies are needed to validate its predictive accuracy in broader populations. Full article

Gestational diabetes mellitus (GDM) occurs in approximately 9–25% of pregnancies and, if left undiagnosed or inadequately controlled, can lead to adverse outcomes for both the mother and the fetus, short and long term. GDM is characterized by glucose intolerance with onset or first recognition during pregnancy and is a multifactorial condition with a pathophysiology that remains incompletely understood. It is strongly associated with a chronic low-grade inflammatory state that contributes to insulin resistance, a hallmark of GDM pathogenesis. Among the fundamental pro-inflammatory cytokines implicated in this process, TNF-α and IL-6 play central roles. TNF-α is a cytokine primarily secreted by activated macrophages, as well as by adipocytes in the context of obesity. Many studies have shown that its levels are elevated in pregnant women with GDM compared to normoglycemic pregnant individuals. IL-6 is another pro-inflammatory cytokine secreted by immune cells, adipose tissue, and the placenta. It is found in higher concentrations in the maternal circulation during pregnancies complicated by GDM. Both TNF-α and IL-6 act synergistically to perpetuate a pro-inflammatory intrauterine environment. Their combined effects exacerbate insulin resistance and may impair pancreatic β-cell compensation during pregnancy, facilitating the onset of GDM in genetically or metabolically susceptible individuals. Recent research has identified various maternal serum biomarkers, such as TNF-α and IL-6, that may hold promise for the early detection of GDM. The aim of our study is to evaluate whether TNF-α and IL-6 can be used as diagnostic tools for the early diagnosis of GDM, allowing for timely intervention and reducing the risk of associated maternal and fetal complications. Full article

Background and Objectives: Gestational diabetes mellitus (GDM) is a complex condition characterized by metabolic disorders of blood glucose that significantly impact the health of both mother and fetus. The objectives of this study were to assess the prevalence and risk factors for maternal and fetal–neonatal complications in women with GDM, comparing them to a control group (pregnant women without GDM) and pregnant women with type 1 diabetes mellitus (T1DM) or type 2 diabetes (T2DM). Materials and Methods: A retrospective observational study was conducted with 1418 pregnant women (279 with GDM, 74 with T1DM, 107 with T2DM, and 958 in the control group). The retrospective data included information on demographics, diagnostic test results, the medical history of pregnant women, treatments administered, identified complications, and other relevant variables for the study’s purpose. Results: Significant differences were found regarding maternal and neo-fetal complications between GDM and the control group in terms of abortion, pregnancy-induced hypertension, and increased fetal weight (macrosomia). Women with T1DM and T2DM showed a higher rate of abortion, premature birth, and an APGAR score of <7 at 5 min compared to those with GDM, and for T1DM, there was a higher rate of fetal mortality than in GDM cases. The primary risk factors for maternal complications included age OR = 1.03 (95% CI: 1.01–1.05, p = 0.002), obesity OR = 2.37 (95% CI: 1.42–3.94, p < 0.001), and chronic hypertension OR = 2.51 (95% CI: 1.26–5.01, p = 0.009). Age and obesity were also significant cofactors for maternal complications. Furthermore, the main significant risk factors for fetal–neonatal complications were obesity OR = 2.481 (95% CI:1.49–4.12, p < 0.001) and chronic hypertension OR = 2.813 (95% CI:1.44–5.49, p = 0.002), both independently and as cofactors. Conclusions: We found that obesity and chronic hypertension are risk factors for both maternal and fetal–neonatal complications. It is essential to prevent and adequately treat these two factors among pregnant women to avoid the onset of GDM. Additionally, screening for GDM is necessary to prevent maternal and fetal complications. Our results highlight the importance of specialized medical care and tailored management protocols in mitigating risks and ensuring positive outcomes for both mother and child during and after childbirth. Full article

Multiple acyl-CoA dehydrogenase deficiency (MADD), also known as glutaric acidemia/glutaric aciduria type II (GA II), is an inborn error of fatty acid, amino acid, and choline metabolism. The chronic management of MADD involves both dietary fat and protein restriction to reduce the substrates of the dehydrogenases affected, the avoidance of prolonged fasting as in any fat metabolism disorder, and monitoring for potential complications. Due to its rarity, there is little published experience on the management of MADD in pregnancy. Herein, we report the successful management of a pregnancy in a patient with late-onset or type III MADD, with considerations for preconception, antepartum, intrapartum, and postpartum care. Full article