Search Results (251)

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

Background/Objectives: Iron stores accrued in utero are critical for fetal and infant neurodevelopment. Low neonatal hemoglobin (Hb) may indicate inadequate iron capture and storage. Prior studies differ on whether and under what conditions maternal anemia predicts neonatal Hb; whether sex differences are present is unknown. Methods: Maternal and neonatal Hb and sociodemographic and health characteristics were abstracted from electronic medical records for biorepository participants at a tertiary academic medical center. Maternal anemia was defined as Hb < 11 g/dL in trimesters T1 and T3 and Hb < 10.5 g/dL in T2. Adjusted linear regression models were used to estimate associations of maternal anemia with neonatal Hb. Sex differences were evaluated with product terms and stratification. Results: In 228 participants with maternal Hb measured, the prevalence of prenatal (pre-delivery) and delivery anemia was 54% and 44%, respectively. Maternal race and ethnicity but no other sociodemographic characteristics were associated with maternal anemia. Neonatal hematology was available for 114 newborns < 7 days old (50%; 52% male). The median (IQR) neonatal Hb was 16.7 g/dL (14.9, 18.0) and did not differ by sex, but it was lower among infants of mothers with vs. without delivery anemia (15.9 vs. 17.1, p = 0.032) and those identifying as Black vs. Hispanic or other (16.0, 17.9, 17.0, respectively; p = 0.003). Independent associations of maternal anemia and race and ethnicity with neonatal Hb were stronger in males and attenuated to null in females. Conclusions: Maternal anemia was highly prevalent and associated sex-specifically with neonatal Hb independent of maternal race and ethnicity. Future studies to replicate these findings with a more comprehensive panel of iron biomarkers are needed. Functional consequences of greater susceptibility to risk factors for low neonatal Hb in male infants need to be further investigated. Full article

Cardiovascular–kidney–metabolic (CKM) syndrome underscores the interconnected biology of cardiovascular disease, kidney disease, and metabolic disorders such as obesity and type 2 diabetes. Although now recognized as a growing global health burden, accumulating preclinical evidence suggests that CKM syndrome may originate in early life—a concept rooted in the developmental origins of health and disease (DOHaD) framework. Animal studies have greatly enhanced our comprehension of these mechanisms, emphasizing the promise of early interventions that focus on antioxidants and gut microbiota modulation to mitigate the development of CKM conditions. Resveratrol, a natural antioxidant and prebiotic, alongside short-chain fatty acids (SCFAs), a postbiotic, have demonstrated the ability to modulate gut microbiota and oxidative stress in experimental models. Various resveratrol derivatives have also been engineered to improve bioavailability, though their effects remain largely confined to animal studies. This review synthesizes preclinical findings on the impact of perinatal oxidative stress and gut dysbiosis on CKM outcomes, critically examining the roles of resveratrol, SCFAs, and their derivatives in animal models. Finally, we highlight the significant translational gap between experimental research and clinical application, underscoring the need for human studies to validate these early-life intervention strategies. Full article

The parathyroid and thymus glands are key components of the endocrine and immune systems, respectively, with intriguing developmental, anatomical, and functional interrelationships. This study starts from the hypothesis that, given their shared embryological origin, it is plausible that the thymus and parathyroid glands interact functionally and may share pathological pathways. The present study explores the developmental pathways, spatial proximity, and potential cross-talk between these glands. Recent studies suggest that parathyroid hormone (PTH) may influence thymic function, including T-cell maturation and immune regulation, while thymic signaling molecules could impact calcium homeostasis and parathyroid activity. Understanding the functional and etiopathogenical relations between these endocrine glands offers new insights into endocrine–immunological crosstalk, and therapeutic approaches targeting disorders such as hypoparathyroidism, thymomas, myasthenia gravis and thymic hypoplasia. Perspectives and conclusion: Future research is essential to discover the molecular mechanisms underpinning this dynamic interrelation and its broader implications for health and disease. Because there is still very little data on this interaction, in-depth studies are necessary on large groups of patients. This research proposes a cross-study of the receptors for the main substances secreted by the two categories of endocrine glands. At the same time, it is essential to carry out an in-depth study on the cervico-pericardial ligaments through the lens of this glandular interaction. These ligaments could contain the main blood and nerve communication pathway between the parathyroids and the glands. Full article

Background/Objectives: Intrauterine growth restriction (IUGR) is associated with enhanced inflammatory activity, poor skeletal muscle glucose metabolism, and pancreatic β cell dysfunction that persist in offspring. We hypothesized that targeting heightened inflammation in IUGR-born neonatal lambs by supplementing anti-inflammatory ω-3 polyunsaturated fatty acids (ω-3 PUFAs) would improve metabolic outcomes. Methods: Maternal heat stress was used to produce IUGR lambs, which received daily oral boluses of ω-3 PUFA Ca²⁺ salts or placebo for 30 days. Results: Greater circulating TNFα and semitendinosus IL6R in IUGR lambs were fully resolved by ω-3 PUFA, and impaired glucose-stimulated insulin secretion, muscle glucose oxidation, and hypertension were partially rescued. Impaired glucose oxidation by IUGR muscle coincided with a greater glycogen content that was completely reversed by ω-3 PUFA and greater lactate production that was partially reversed. Ex vivo O₂ consumption was increased in IUGR muscle, indicating compensatory lipid oxidation. This too was alleviated by ω-3 PUFA. Conversely, ω-3 PUFA had little effect on IUGR-induced changes in lipid flux and hematology parameters, did not resolve greater muscle TNFR1, and further reduced muscle β2-adrenoceptor content. Conclusions: These findings show that targeting elevated inflammatory activity in IUGR-born lambs in the early neonatal period improved metabolic outcomes, particularly muscle glucose metabolism and β cell function. Full article

Pediatric chronic kidney disease (CKD) is a growing concern that often originates early in life, yet significant challenges remain in translating clinical guidelines into real-world practice. World Kidney Day 2025 highlights the importance of early detection, but the three levels of preventive strategies commonly recommended for adults may not be directly applicable to children. Unlike adult CKD, primary prevention in pediatrics should focus on prenatal, neonatal, and early-life factors such as congenital anomalies of the kidney and urinary tract (CAKUT), preterm birth, maternal health, and environmental exposures. Secondary prevention, involving early detection through screening, is crucial, yet the effectiveness of mass urinary screening in children remains a subject of global debate. Several key challenges persist, including the accurate estimation of glomerular filtration rate (eGFR), consistent definition and diagnosis of pediatric hypertension, identification of reliable biomarkers, and targeted screening in specific pediatric populations. Although clear guidelines exist to manage CKD progression and enhance quality of life, a critical gap remains between what is known and what is practiced. Closing this gap requires robust evidence to inform best practices, improve health-related quality of life, and advance pediatric kidney replacement therapies. To protect and improve kidney health for every child worldwide, these challenges must be acknowledged, and sustainable, evidence-based solutions must be developed and implemented without further delay. Full article

Epidemiological evidence firmly supports the rationale that chronic diseases demonstrate a heritability component. Notwithstanding recent advances in genomic technologies, in a significant proportion of heritable diseases, a candidate gene of interest that explains the entire picture of heritability remains to be identified. Further epidemiological evidence points to environmental risk factors contributing to chronic disease prevalence and severity. The Developmental Origins of Health and Disease hypothesis points to epigenetics as the mechanism modulating gene–environment interactions to elicit disease. Yet the primary effector of epigenetic inheritance remains to be elucidated. This review focuses on key contributors to mammalian development and the epigenetic changes measured therein, to draw attention towards potential molecular candidates underpinning chronic disease heritability. Full article

The visual system has served as an expeditious entry point for discerning the mechanism of action of many brain systems, spearheading multiple fields of neuroscience in the process. It has additionally launched the careers of countless scientists, as we have crafted new means to understand neuronal structures and their functions, leading to advances in many areas of the sciences. Indeed, one can readily mark the onset of the scientific examination of the visual system with the 1851 invention of the ophthalmoscope by Hermann von Helmholtz, and the trichromatic theory of color vision in 1802. The Young–Helmholtz understanding the red–green–blue nature of color vision became the foundation to understanding sensory system function that visual artists and also contemporary flat panel displays rely on. It is fascinating to realize that the paintings of Georges Seurat and an iPhone display share a commonality of this application of the trichromatic theory. While it was not until 1956 that the existence of cells responsive to three different ranges of wavelengths was proven with the work of Gunnar Svaetichin, this proof in many ways marked the advancement of tools to visualize at a microscopic level, a full century after the Young–Helmholtz theory was developed. Just a decade later, in 1966, the person widely considered as the founder of modern neuroscience, Stephen Kuffler, founded the Harvard neurobiology department. It was from Kuffler’s work with his post-doctoral students that many new fields of study were created and from whom many of the neuroscience programs across the US were founded. In terms of the visual system, Kuffler and his team were key in detailing areas of retinal neuroanatomy, neurochemistry, neurophysiology, and developmental neurobiology. This paper traces areas in visual system research that provide our understanding of the disparate areas of brain sciences. As such, there are six categories that are evaluated, each of which spawned work in multiple areas that have become mainstays in neuroscience. These range from fields that were dominant a half century ago to ones that have their origins in this decade. The commonality is that all of these owe their origin to Helmholtz and Kuffler, polymaths of the nineteenth and twentieth centuries. We will examine the impact of vision research across the following fields of neuroscience: sensory system function, neuroanatomy, neurochemistry, neurophysiology, developmental neurobiology, and neurological health and disease. Full article

Kidney disease and hypertension are interconnected, prevalent conditions that affect both pregnant women and children. Oxidative stress occurs when reactive oxygen species or reactive nitrogen species exceed the capacity of antioxidant systems. It plays a critical role in kidney development, resulting in kidney programming and increased risks for kidney disease and hypertension across the life course. Animal models have significantly advanced our understanding of oxidative stress-related kidney programming, the molecular mechanisms involved, and early-life antioxidant interventions to prevent kidney disease. This review critically examines the influence of perinatal oxidative stress on kidney development, highlighting its long-term effects on kidney outcomes and susceptibility to hypertension. It also explores the potential of antioxidant-based interventions in preventing kidney disease and hypertension. Furthermore, the review addresses the existing gap between insights gained from animal models and their translation into clinical practices, emphasizing the challenges and opportunities for future research in this area. Full article

The global incidence and prevalence of cardiometabolic disorders have risen significantly in recent years. Although lifestyle choices in adulthood play a crucial role in the development of these conditions, it is well established that events occurring early in life can have an important effect. Recent research on cardiometabolic diseases has highlighted the influence of sexual dimorphism on risk factors, underlying mechanisms, and response to therapies. In this narrative review, we summarize the current understanding of sexual dimorphism in cardiovascular and metabolic diseases in the general population and within the framework of the Developmental Origins of Health and Disease (DOHaD) concept. We explore key risk factors and mechanisms, including the influence of genetic and epigenetic factors, placental and embryonic development, maternal nutrition, sex hormones, energy metabolism, microbiota, oxidative stress, cell death, inflammation, endothelial dysfunction, circadian rhythm, and lifestyle factors. Finally, we discuss some of the main therapeutic approaches, responses to which may be influenced by sexual dimorphism, such as antihypertensive and cardiovascular treatments, oxidative stress management, nutrition, cell therapies, and hormone replacement therapy. Full article

The benefits of breastfeeding for both mother and infant are generally recognized; however, the connections between breast milk, lactation, and long-term offspring health and disease remain incompletely understood. Cardiovascular–kidney–metabolic syndrome (CKMS) has become a major global public health challenge. Insufficient breast milk supply, combined with various early-life environmental factors, markedly increases the future risk of CKMS, as highlighted by the developmental origins of health and disease (DOHaD) concept. Given its richness in nutrients and bioactive components essential for infant health, this review focuses on reprogramming strategies involving breast milk to improve offspring’s cardiovascular, kidney, and metabolic health. It also highlights recent experimental advances in understanding the mechanisms driving CKMS programming. Cumulatively, the evidence suggests that lactational impairment heightens the risk of CKMS development. In contrast, early interventions during the lactation period focused on animal models that leverage breast milk components in response to early-life cues show potential in improving cardiovascular, kidney, and metabolic outcomes—an area warranting further investigation and clinical translation. Full article

Background: Gestational diabetes mellitus (GDM), characterized by gestational hyperglycemia due to insufficient insulin response, poses significant risks to both maternal and offspring health. Fetal exposure to maternal hyperglycemia leads to short-term complications such as macrosomia and neonatal hypoglycemia and long-term risks including obesity, metabolic syndrome, cardiovascular dysfunction, and type 2 diabetes. The Developmental Origins of Health and Disease (DOHaD) theory explains how maternal hyperglycemia alters fetal programming, increasing susceptibility to metabolic disorders later in life. Objective: This review explores the intergenerational impact of GDM, linking maternal hyperglycemia to lifelong metabolic, cardiovascular, and neurodevelopmental risks via epigenetic and microbiome alterations. It integrates the most recent findings, contrasts diagnostic methods, and offers clinical strategies for early intervention and prevention. Methods: A comprehensive literature search was conducted in PubMed, Scopus, and ScienceDirect to identify relevant studies published between 1 January 2000 and 31 December 2024. The search included studies focusing on the metabolic and developmental consequences of GDM exposure in offspring, as well as potential mechanisms such as epigenetic alterations and gut microbiota dysbiosis. Studies examining preventive strategies and management approaches were also included. Key Findings: Maternal hyperglycemia leads to long-term metabolic changes in offspring, with epigenetic modifications and gut microbiota alterations playing key roles. GDM-exposed children face increased risks of obesity, glucose intolerance, and cardiovascular diseases. Early screening and monitoring are crucial for risk reduction. Practical Implications: Understanding the intergenerational effects of GDM has important clinical implications for prenatal and postnatal care. Early detection, lifestyle interventions, and targeted postnatal surveillance are essential for reducing long-term health risks in offspring. These findings emphasize the importance of comprehensive maternal healthcare strategies to improve long-term outcomes for both mothers and their children. Full article

Introduction: Early-life neurological and inflammatory disorders significantly affect long-term cognitive, social, and emotional development. The ‘Developmental Origins of Health and Disease’ hypothesis states that an adverse intrauterine environment may predispose offspring to chronic health conditions due to altered growth and development. Factors measured in umbilical cord blood can provide information about the status of the in utero environment during development. Evidence indicates that umbilical cord blood adipokines, namely leptin and adiponectin, may influence fetal programming and could be useful in predicting offspring health outcomes. Leptin and adiponectin are crucial in energy homeostasis, immune response, and placental function, and some studies suggest that altered concentrations may increase the risk of developing inflammatory and neurological disorders in later life. Further, limited studies have demonstrated sex-specific differences in adipokine concentrations and disease risk. Conclusions: Understanding the role of umbilical cord blood adipokines in fetal programming could offer new insights into early risk prediction and intervention strategies, promoting better health outcomes for children at risk of neurological and inflammatory diseases due to an adverse maternal environment during pregnancy. Full article

We are exposed to a variety of environmental chemicals in our daily lives. It is possible that the effects of this daily chemical exposure could accumulate in the organism in some form and influence health and disease development. The exposure effects extend throughout the human lifetime, not only after birth, but also during the embryonic period. Epigenetics is an important target for the molecular mechanisms of daily environmental chemical effects. Epigenetics is a mechanism of gene transcription regulation that does not involve changes in DNA sequence. The Developmental Origins of Health and Disease (DOHaD) theory has also been proposed, in which effects such as exposure to environmental chemicals during embryonic period are mediated by epigenetic changes, which may lead to risk for disease development and adverse health effects after maturity. This review summarizes the association between embryonic exposure and the epigenetics of well-known non-essential toxic heavy metals (methylmercury, cadmium, arsenic, and lead), a representative group of environmental chemicals. In the future, it will be important to predict the epigenetic mechanisms of unknown chemical and combined exposures. In addition, further experimental investigations using experimental animals and the accumulation of knowledge are needed to study the transgenerational effects of environmental chemicals in the future. Full article

Cardiovascular–kidney–metabolic syndrome (CKMS) has become a significant global health challenge. Since CKMS often originates early in life, as outlined by the developmental origins of health and disease (DOHaD) concept, prevention is a more effective strategy than treatment. Various animal models, classified by environmental exposures or mechanisms, are used to explore the developmental origins of CKMS. However, no single model can fully replicate all aspects of CKMS or its clinical stages, limiting the advancement of preventive and therapeutic strategies. This review aims to assist researchers by comparing the strengths and limitations of common animal models used in CKMS programming studies and highlighting key considerations for selecting suitable models. Full article