Search Results (18)

Background/Objectives: Cord blood mitochondrial DNA copy number (mtDNAcn) has been proposed as a biomarker reflecting environmental influences during fetal life, with reported associations with perinatal outcomes such as birth weight and length. Within the framework of the Developmental Origins of Health and Disease (DOHaD) theory, this study aimed to investigate whether cord blood mtDNAcn is related to postnatal physical growth in early childhood. Methods: We analyzed data from 150 newborns (68 females and 82 males) enrolled in the Tohoku Medical Megabank Birth and Three-Generation Cohort Study in Japan. Cord blood mtDNAcn was quantified using real-time PCR, and standard deviation scores for weight and height were assessed at 1, 2–3, 4–6, 18–24, and 36–48 months of age. Correlation analyses were conducted separately by sex. Results: Cord blood mtDNAcn showed no significant associations with body weight or height at any of the postnatal time points up to 48 months of age. Growth trajectories of infants with higher or lower mtDNAcn values at birth tended to converge toward the population mean during infancy and toddlerhood. Conclusions: Although no significant relationships were observed, this exploratory, hypothesis-generating study provides a foundation for future investigations. Larger cohorts with extended follow-up are needed to clarify the potential significance of cord blood mtDNAcn in early-life research on child growth and health. Full article

Research has identified fetal risk factors for adult diseases, forming the basis for the Developmental Origins of Health and Disease (DOHaD) hypothesis. DOHaD suggests that maternal insults during pregnancy cause structural and functional changes in fetal organs, increasing the risk of chronic diseases like type 2 diabetes mellitus (T2DM) in adulthood. It is proposed that altered maternal physiology, such as increased glucocorticoid (GC) levels associated with a dysregulated hypothalamic-pituitary-adrenal (HPA) axis in maternal stress and T2DM during pregnancy, exposes the fetus to excess GC. Prenatal glucocorticoid exposure reduces fetal growth and programs the fetal HPA axis, permanently altering its activity into adulthood. This programmed HPA axis is linked to increased risks of hypertension, cardiovascular diseases, and mental disorders in adulthood. With the global rise in T2DM, particularly among young adults of reproductive age, it is crucial to prevent its onset. T2DM is often preceded by a prediabetic state, a condition that does not show any symptoms, causing many to unknowingly progress to T2DM. Studying prediabetes is essential, as it is a reversible stage that may help prevent T2DM-related pregnancy complications. The existing literature focuses on HPA axis dysregulation in T2DM pregnancies and its link to fetal programming. However, the effects of prediabetes on HPA axis function, specifically glucocorticoid in pregnancy and fetal outcomes, are not well understood. This review consolidates research on T2DM during pregnancy, its impact on fetal programming via the HPA axis, and possible links with pregestational prediabetes. Full article

The developmental origin of health and disease (DOHaD) hypothesis refers to the adverse effects of suboptimal developmental environments during embryonic and early fetal stages on the long-term health of offspring. Intrauterine metabolic perturbations can profoundly impact organogenesis in offspring, particularly affecting cardiac development and giving rise to potential structural and functional abnormalities. In this discussion, we contemplate the existing understanding regarding the impact of maternal metabolic disorders, such as obesity, diabetes, or undernutrition, on the developmental and functional aspects of the offspring’s heart. This influence has the potential to contribute to the susceptibility of offspring to cardiovascular health issues. Alteration in the nutritional milieu can influence mitochondrial function in the developing hearts of offspring, while also serving as signaling molecules that directly modulate gene expression. Moreover, metabolic disorders can exert influence on cardiac development-related genes epigenetically through DNA methylation, levels of histone modifications, microRNA expression, and other factors. However, the comprehensive understanding of the mechanistic underpinnings of these phenomena remains incomplete. Further investigations in this domain hold profound clinical significance, as they can contribute to the enhancement of public health and the prevention of cardiovascular diseases. Full article

In premature infants receiving parenteral nutrition, oxidative stress is a trigger for the development of bronchopulmonary dysplasia, which is an important factor in the development of adult lung diseases. Neonatal vitamin C and glutathione deficiency is suspected to induce permanent modification of redox metabolism favoring the development of neonatal and adult lung diseases. A total of 64 3-day-old guinea pigs were fed an oral diet that was either complete or deficient in vitamin C (VCD), cysteine (CD) (glutathione-limiting substrate) or both (DD) for 4 days. At 1 week of age, half of the animals were sacrificed while the other started a complete diet until 12 weeks of age. At 1 week, the decrease in lung GSH in all deficient groups was partially explained by the oxidation of liver methionine-adenosyltransferase. mRNA levels of kelch-like ECH-associated protein 1 (Keap1), glutathione-reductase (Gsr) and glutaredoxin-1 (Glrx) were significantly lower only in CD but not in DD. At 12 weeks, glutathione levels were increased in VCD and CD. Keap1, Gsr and Glrx mRNA were increased, while glutathione-reductase and glutaredoxin proteins were lower in CD, favoring a higher glutathionylation status. Both neonatal deficiencies result in a long-term change in glutathione metabolism that could contribute to lung diseases’ development. Full article

The prevalence of poor metabolic health is growing exponentially worldwide. This condition is associated with complex comorbidities that lead to a compromised quality of life. One of the contributing factors recently gaining attention is exposure to environmental chemicals, such as endocrine-disrupting chemicals (EDCs). Considerable evidence suggests that EDCs can alter the endocrine system through immunomodulation. More concerning, EDC exposure during the fetal development stage has prominent adverse effects later in life, which may pass on to subsequent generations. Although the mechanism of action for this phenomenon is mostly unexplored, recent reports implicate that non-coding RNAs, such as microRNAs (miRs), may play a vital role in this scenario. MiRs are significant contributors in post-transcriptional regulation of gene expression. Studies demonstrating the immunomodulation of EDCs via miRs in metabolic health or towards the Developmental Origins of Health and Disease (DOHaD) Hypothesis are still deficient. The aim of the current review was to focus on studies that demonstrate the impact of EDCs primarily on innate immunity and the potential role of miRs in metabolic health. Full article

(1) Background: The developmental origins of health and disease (DOHaD) hypothesis links adverse fetal exposures with developmental mal-adaptations and morbidity later in life. Short- and long-term exposures to air pollutants are known contributors to health outcomes; however, the potential for developmental health effects of air pollution exposures during gestation or early-childhood have yet to be reviewed and synthesized from a DOHaD lens. The objective of this study is to summarize the literature on cardiovascular and metabolic, respiratory, allergic, and neuropsychological health outcomes, from prenatal development through early childhood, associated with early-life exposures to outdoor air pollutants, including traffic-related and wildfire-generated air pollutants. (2) Methods: We conducted a search using PubMed and the references of articles previously known to the authors. We selected papers that investigated health outcomes during fetal or childhood development in association with early-life ambient or source-specific air pollution exposure. (3) Results: The current literature reports that prenatal and early-childhood exposures to ambient and traffic-related air pollutants are associated with a range of adverse outcomes in early life, including cardiovascular and metabolic, respiratory and allergic, and neurodevelopmental outcomes. Very few studies have investigated associations between wildfire-related air pollution exposure and health outcomes during prenatal, postnatal, or childhood development. (4) Conclusion: Evidence from January 2000 to January 2022 supports a role for prenatal and early-childhood air pollution exposures adversely affecting health outcomes during development. Future studies are needed to identify both detrimental air pollutants from the exposure mixture and critical exposure time periods, investigate emerging exposure sources such as wildfire, and develop feasible interventional tools. Full article

Mammals can obtain taurine from food and synthesize it from sulfur-containing amino acids. Mammalian fetuses and infants have little ability to synthesize taurine. Therefore, they are dependent on taurine given from mothers either via the placenta or via breast milk. Many lines of evidence demonstrate that maternally derived taurine is essential for offspring development, shaping various traits in adults. Various environmental factors, including maternal obesity, preeclampsia, and undernutrition, can affect the efficacy of taurine transfer via either the placenta or breast milk. Thus, maternally derived taurine during the perinatal period can influence the offspring’s development and even determine health and disease later in life. In this review, I will discuss the biological function of taurine during development and the regulatory mechanisms of taurine transport from mother to offspring. I also refer to the possible environmental factors affecting taurine functions in mother-offspring bonding during perinatal periods. The possible functions of taurine as a determinant of gut microbiota and in the context of the Developmental Origins of Health and Disease (DOHaD) hypothesis will also be discussed. Full article

Depression is one of the most common mental disorders in the general population, and multiple mechanisms are involved in the etiology of this disease, including myelination. According to the Developmental Origins of Health and Disease (DOHaD) hypothesis, maternal diet affects the lifetime of the individual during adulthood and may contribute to the development of neuropsychiatric disorders. Additionally, the intensive processes of myelination contribute to the development of the central nervous system in the perinatal period, while any alterations during this crucial process providing the physiological functioning of neurons may lead to neuropsychiatric disorders in the next generation. The present review summarizes the current knowledge on the role of the myelin-related changes in depression, as well as the crosstalk among maternal malnutrition, myelination, and depression in preclinical and clinical settings. Full article

The “developmental origins of health and disease” (DOHaD) hypothesis refers to the influence of early developmental exposures and fetal growth on the risk of chronic diseases in later periods. During fetal and early postnatal life, cell differentiation and tissue formation are influenced by several factors. The interaction between genes and environment in prenatal and early postnatal periods appears to be critical for the onset of multiple diseases in adulthood. Important factors influencing this interaction include genetic predisposition, regulation of gene expression, and changes in microbiota. Premature birth and intrauterine growth restriction (IUGR) are other important factors considered by the DOHaD hypothesis. Preterm birth is associated with impaired or arrested structural or functional development of key organs/systems, making preterm infants vulnerable to cardiovascular, respiratory, and chronic renal diseases during adulthood. Growth restriction, defined as impaired fetal growth compared to expected biological potential in utero, is an additional negative factor increasing the risk of subsequent diseases. Environmental factors implicated in the developmental programming of diseases include exposure to pollution, stress, drugs, toxic agents, nutrition, and exercise. The DOHaD may explain numerous conditions, including cardiovascular, metabolic, respiratory, neuropsychiatric, and renal diseases. Potential antenatal and postnatal preventive measures, interventions, and future directions are discussed. Full article

Background/Aims: Epigenetic regulation is considered the main molecular mechanism underlying the developmental origin of health and disease’s (DOHAD) hypothesis. Previous studies that have investigated the role of paternal exercise on the metabolic health of the offspring did not control for the amount and intensity of the training or possible effects of adaptation to exercise and produced conflicting results regarding the benefits of parental exercise to the next generation. We employed a precisely regulated exercise regimen to study the transgenerational inheritance of improved metabolic health. Methods: We subjected male mice to a well-controlled exercise -training program to investigate the effects of paternal exercise on glucose tolerance and insulin sensitivity in their adult progeny. To investigate the molecular mechanisms of epigenetic inheritance, we determined chromatin markers in the skeletal muscle of the offspring and the paternal sperm. Results: Offspring of trained male mice exhibited improved glucose homeostasis and insulin sensitivity. Paternal exercise modulated the DNA methylation profile of PI3Kca and the imprinted H19/Igf2 locus at specific differentially methylated regions (DMRs) in the skeletal muscle of the offspring, which affected their gene expression. Remarkably, a similar DNA methylation profile at the PI3Kca, H19, and Igf2 genes was present in the progenitor sperm indicating that exercise-induced epigenetic changes that occurred during germ cell development contributed to transgenerational transmission. Conclusion: Paternal exercise might be considered as a strategy that could promote metabolic health in the offspring as the benefits can be inherited transgenerationally. Full article

Non-communicable diseases (NCDs) sauch as diabetes, obesity and cardiovascular diseases are rising rapidly in all countries world-wide. Environmental maternal factors (e.g., diet, oxidative stress, drugs and many others), maternal illnesses and other stressors can predispose the newborn to develop diseases during different stages of life. The connection between environmental factors and NCDs was formulated by David Barker and colleagues as the Developmental Origins of Health and Disease (DOHaD) hypothesis. In this review, we describe the DOHaD concept and the effects of several environmental stressors on the health of the progeny, providing both animal and human evidence. We focus on cardiovascular diseases which represent the leading cause of death worldwide. The purpose of this review is to discuss how in vitro studies with pluripotent stem cells (PSCs), such as embryonic and induced pluripotent stem cells (ESC, iPSC), can underpin the research on non-genetic heart conditions. The PSCs could provide a tool to recapitulate aspects of embryonic development “in a dish”, studying the effects of environmental exposure during cardiomyocyte (CM) differentiation and maturation, establishing a link to molecular mechanism and epigenetics. Full article

Developmental programming of chronic diseases by perinatal exposures/events is the basic tenet of the developmental origins hypothesis of adult disease (DOHaD). With consumption of fructose becoming more common in the diet, the effect of fructose exposure during pregnancy and lactation is of increasing relevance. Human studies have identified a clear effect of fructose consumption on maternal health, but little is known of the direct or indirect effects on offspring. Animal models have been utilized to evaluate this concept and an association between maternal fructose and offspring chronic disease, including hypertension and metabolic syndrome. This review will address the mechanisms of developmental programming by maternal fructose and potential options for intervention. Full article

Genomic imprinting is an epigenetic mechanism that results in monoallelic, parent-of-origin-specific expression of a small number of genes. Imprinted genes play a crucial role in mammalian development as their dysregulation result in an increased risk of human diseases. DNA methylation, which undergoes dynamic changes early in development, is one of the epigenetic marks regulating imprinted gene expression patterns during early development. Thus, environmental insults, including endocrine disrupting chemicals during critical periods of fetal development, can alter DNA methylation patterns, leading to inappropriate developmental gene expression and disease risk. Here, we summarize the current literature on the impacts of in utero exposure to endocrine disrupting chemicals on genomic imprinting and metabolism in humans and rodents. We evaluate how early-life environmental exposures are a potential risk factor for adult metabolic diseases. We also introduce our mouse model of phthalate exposure. Finally, we describe the potential of genomic imprinting to serve as an environmental sensor during early development and as a novel biomarker for postnatal health outcomes. Full article

Mitochondrial dysfunction is known to contribute to mitochondrial diseases, as well as to a variety of aging-based pathologies. Mitochondria have their own genomes (mitochondrial DNA (mtDNA)) and the abnormalities, such as point mutations, deletions, and copy number variations, are involved in mitochondrial dysfunction. In recent years, several epidemiological studies and animal experiments have supported the Developmental Origin of Health and Disease (DOHaD) theory, which states that the environment during fetal life influences the predisposition to disease and the risk of morbidity in adulthood. Mitochondria play a central role in energy production, as well as in various cellular functions, such as apoptosis, lipid metabolism, and calcium metabolism. In terms of the DOHaD theory, mtDNA copy number may be a mediator of health and disease. This paper summarizes the results of recent epidemiological studies on the relationship between environmental factors and mtDNA copy number during pregnancy from the perspective of DOHaD theory. The results of these studies suggest a hypothesis that mtDNA copy number may reflect environmental influences during fetal life and possibly serve as a surrogate marker of health risks in adulthood. Full article