Journal of Developmental Origins of Health and Disease最新文献

Studies have linked lower birth weight to development of radiographic osteoarthritis (OA). We examined early life factors in relation to subsequent knee pain among individuals with radiographic OA. 143 participants from the UK Hertfordshire Cohort study were included. Birth weight and weight at one year (WA1) were ascertained from health ledgers and used to derive conditional infant weight gain (CIWG). At baseline and follow-up, heath questionnaires (including knee pain) and knee radiographs were collected. Only those with radiographic knee OA at baseline were analysed. Logistic regression was used to examine early life factors in relation to pain. Pain at follow-up was common (men 41.3%, women 50%). Greater WA1 and greater CIWG were related to reduced risk of knee pain at follow-up after adjustment for sex and follow-up time. CIWG was protective against knee pain at follow-up, with this association attenuated after adjustment for follow-up osteophyte score. Validation in larger studies is required.

The prenatal period, childhood, and adolescence are critical periods of development characterized by high plasticity. As an extension of the Developmental Origins of Health and Disease (DOHaD) paradigm, known as Origins of Paternal Health and Disease (POHaD), recent studies in rodents provide evidence that paternal obesity is associated not only with infertility but also with an increased risk of metabolic disorders in the offspring. In rodents, litter size reduction is used to induce lactational overfeeding by increasing the amount of breast milk to pups, which causes metabolic and reproductive disorders in adulthood. This work evaluated the metabolic and reproductive alterations in the offspring of males raised in normal or small litter (SL) in the prepubertal period and in adult life. The results show that paternal obesity due to early overfeeding affects the offspring in a sex-specific manner. During the prepubertal period, male offspring of SL fathers showed decreased Lee index, tibia length, and HDL plasma levels, and increased weight of gastrocnemius muscle, while female offspring of SL fathers only showed reduced HDL plasma levels. In adulthood, male offspring of overfed males showed glucose intolerance and reduced food intake and triglycerides plasma levels, signs of metabolic dysfunction. Female offspring of overfed males showed delayed puberty onset and higher prevalence of infertile periods in the estrous cycles, indicating a potential susceptibility to reproductive dysfunction. The results of the current study show that paternal obesity due to early overfeeding affects energy balance and reproduction of their offspring in a sex-specific manner.

Obesity and overweight in pregnant women increase pregnancy and neonatal morbidity with a risk of metabolic syndrome for children in later life. Maternal preconceptional bariatric surgery reduces maternal and paediatric outcomes but may induce fetal nutritional deficiencies and intrauterine growth restriction through placental reprogramming. The aim of this study was to describe feto-placental unit modifications induced by obesity, and the effect of bariatric surgery performed before gestation, on a diet-induced obese rat model. One month after surgery, rats of 'control', 'obese' and 'bariatric surgery' groups were mated and then sacrificed at D19 of gestation. Clinical description, immuno-histochemistry and molecular analyses were performed on feto-placental units. Obesity induces placental modifications including lipid accumulations, increased inflammation and oxidative stress. Some of these modifications are partially restored by maternal preconceptional bariatric surgery. On the other hand, a reduction in the expression of markers of glucose transport, insulin function and amino acid transport, after bariatric surgery was observed. This phenotype may lead to fetal caloric restriction, adoption of a 'thrifty phenotype' and subsequently fetal growth restriction. These preliminary findings highlight the importance of a close follow-up of women who have undergone bariatric surgery and their children.

Early life stress (ELS) increases the risk of metabolic disorders such as obesity, as well as neuropsychiatric conditions including depression. Adolescence represents a critical window for metabolic programming, particularly under the influence of ELS and poor dietary habits. Animal models of ELS, such as maternal separation (MS180), induce long-term alterations in hypothalamic-pituitary-adrenal (HPA) axis function, glucose metabolism, and emotionality; however, it remains unclear whether this paradigm increases vulnerability to a chronic metabolic challenge. The aim of this study was to evaluate the effects of MS180 on male rats provided with mild fructose in drinking water starting at postnatal day (P) 21. Control and MS180 (3 h daily, from postnatal day 1 to day 14) rats were given a choice of normal water or a 10% fructose solution for 10 weeks, with standard animal facility-reared (STD) animals serving as controls. Innate emotionality was assessed using the forced swimming test. Animals were implanted with a jugular vein catheter and we evaluated fasting glucose, glucose tolerance, and baseline corticosterone (CORT) levels after one week. Our findings showed that only MS180 + Fructose rats showed a decrease in swimming and increased immobility in the forced swimming test, and previously reported effects of MS180 were only observed when performing simple comparisons. MS180 also increased body weight gain, caloric intake, impaired glucose tolerance, and elevated baseline CORT levels; however, these effects were not exacerbated by fructose. These findings suggest that even low-level fructose exposure during periadolescence may exacerbate behavioral, but not metabolic, vulnerabilities induced by ELS.

Brain development and face morphology are related through underlying biological mechanisms, namely embryonic neuroectodermal processes. This study examined whether the facial parameters identified in children can help understand the neurodevelopmental impact of prenatal exposures on child behavior. We studied 9- to 10-year-old children of European descent from Generation R Study (N = 2,779) with three-dimensional face photographs. With an AI model of a 3D graph autoencoder, each facial shape was compressed into 200 traits representing facial morphology. We examined associations of traits with internalizing and externalizing behaviors and attention problems. Next, select prenatal substance and micronutrient exposures were related to facial traits using adjusted linear regression analyses. We identified a robust association between one specific facial trait and attention problem scores (β = -1.47, p = 0.038). This trait features chin retrusion, mild nasal contour variation, nose tip protrusion, and overall facial asymmetry. Higher prenatal vitamin D and folic acid concentrations were associated with more facial curvature (β = 0.0001, 95%CI: 0.00001 to 0.0002, p = 0.002; and β = 0.0003, 95%CI: 0.00002 to 0.0005, p = 0.03 accordingly), while prenatal tobacco smoking showed a negative association both until the mother became aware of pregnancy (β = -0.008, 95%CI: -0.0135 to -0.0014, p = 0.02) and throughout pregnancy (β = -0.006, 95%CI: -0.0113 to -0.0005, p = 0.03). Findings suggest that facial morphology may serve as a marker of impaired neuroectodermal development. Leveraging its association with attention problems enabled a robust examination of prenatal exposures' impact. The associations of maternal smoking, vitamin D, and folic acid concentrations with facial morphology provide insights into the origins of neurodevelopment.

Maternal deficiency of vitamin B12 (B12) is associated with neural tube defects, fetal growth restriction, and future risk of non-communicable disease in the offspring. Little is known about the molecular basis of these associations. We hypothesized that B12 regulates the expression of fetal genes, thereby influencing fetal growth and fetal programming. We investigated the association of B12 and other micronutrient concentrations in the cord blood with gene expression in the cord blood mononuclear cells. We performed a Weighted Gene Co-expression Network Analysis (WGCNA) on cord blood transcriptome of babies born in a pre-conception trial Pune Rural Intervention in Young Adolescents of B12 and multi-micronutrients (MMN). The gene modules (clusters) in WGCNA that showed a significant correlation with cord blood B12 and MMN were subjected to gene ontology (GO) analysis. WGCNA generated 23 different modules. Cord blood B12 concentrations were strongly correlated with modules of genes involved in methylation reactions and gene regulation. Cord B2 concentrations correlated with gene modules associated with demethylation reactions. Vitamins B6 and B9 did not show a unique association either with gene modules or specific GO terms. Our results demonstrate that maternal B12 may regulate expression of fetal genes involved in methylation reaction. This is a novel suggestion for the role of B12 in fetal growth, development, and the Developmental Origins of Health and Disease paradigm.

Research into the Developmental Origins of Health and Disease (DOHaD) has established links between environmental exposures in early life and later-life health outcomes. Emerging interventions typically focus on improving maternal nutrition and neonatal healthcare practices yet often neglect to assess or enhance subject understanding of potential long-term impacts or to communicate the benefits of maximising parental health prior to conception. This study critically evaluates a survey tool developed to measure knowledge of non-communicable diseases (NCDs) and early-life contributors to lifelong health. The rationale behind the wording and format of the questions is examined alongside options for coding and statistical interpretation of the data. Considerations for implementation are discussed, illustrated by key findings arising from tracking of the tool's application in Aotearoa New Zealand over ten years. We demonstrate that the survey tool can be adapted for use in a variety of contexts, producing both quantitative and qualitative baseline data suitable for informing health promotion interventions and monitoring changes in population knowledge. This research also highlights a key difference between awareness of and understanding of scientific concepts and the importance of distinguishing between these when considering public engagement with science.

In a normal pregnancy, glucocorticoids (GC), such as cortisol, play an essential role in early heart development. GC concentrations surge in late gestation to facilitate the maturation of fetal systems in preparation for birth. However, pregnancy complications related to stress, lifestyle factors, disease, and commonly used antenatal care treatments (GC therapy and artificial reproductive technology) can lead to prematurely increased GC concentrations that are detrimental to the heart before it is mature enough to benefit. These findings underpin the hypothesis that GC play a double-edged role that benefits normal heart development but is potentially harmful when dysregulated. However, the mechanisms by which both physiological and pathological elevations in GC concentrations influence the fetal cardiometabolic pathways that lead to detrimental long-term cardiovascular outcomes remain unclear. This review will, firstly, describe how cortisol regulates different aspects of cardiac development and, secondly, compare findings from different animal models that have provided mechanistic insight into how excess cortisol/GC during pregnancy impacts cardiac health across the life course.

The fetus and neonate are especially vulnerable to toxic effects of polychlorinated biphenyls (PCBs), that have been shown to perturb behavioral and neuropsychological development. This study aimed to examine the long-term effects of developmental exposure to PCBs. Doses selected were environmentally relevant to those found in epidemiological studies, on the central nervous system (CNS) of adult rat offspring. Pregnant Sprague Dawley rats were fed cookies that contained a mixture of fourteen PCBs or vehicle (corn oil) daily. PCB doses were 0.011 mg/kg maternal body weight/day ("low") or 1.10 mg/kg maternal body weight/day ("high"), for 42 days throughout gestation and lactation. Adult offspring were euthanized on postnatal day 450. A battery of immunohistochemical markers of brain structure and function were selected to assess possible effects of developmental PCB exposure. Using a 3×2 factorial design (treatment and sex), two-way analysis of variance revealed significant effects of treatment through the CNS, with no main effect of sex or interaction effects. In comparison with controls, both low and high dose developmental PCB exposure significantly (p < 0.05) increased inhibitory enzyme glutamic acid decarboxylase (GAD67) immunoreactivity in the cerebellar vermis, and decreased lipofuscin autofluorescence in the locus coeruleus (LC). Low dose developmental PCB exposure significantly decreased the perimeter of endothelial cells in the periaqueductal gray, ventral orbitofrontal cortex; and decreased lipofuscin in the dorsal striatum, compared to controls. Findings support the Developmental Origins of Health and Disease concept, which broadly posits that early-life perturbations may influence health trajectories over the lifespan.