Journal of Developmental Origins of Health and Disease最新文献

Childbirth influences maternal and new-born's future health, with the Epigenetic Impact of Childbirth (EPIIC) hypothesis proposing that labour stress affects foetal gene expression. This study explores how birth experiences relate to DNA methylation in infants, breastfeeding and mother-infant bonding. Data from the Avon Longitudinal Study of Parents and Children was used, including 14,541 pregnant women. The ARIES subset of 1,022 mother-child pairs provided DNA methylation profiles. Maternal birth experience (MBE) was evaluated, with mother-infant bonding and breastfeeding. Statistical analysis involved linear regression and epigenome-wide association study. Half of the mothers reported at least one negative childbirth event, with 7% experiencing three or more adverse events. Negative MBE correlated with shorter breastfeeding duration and weaker mother-infant bonding. No significant CpG associations with MBE were found. While positive MBE is linked to improved mother-infant bonding and breastfeeding, no significant changes in DNA methylation profiles were observed in the offspring. Further research is needed to understand MBE's long-term impact on child health.

Seasonal variation in maternal exposure to sunlight during pregnancy, which relates to variation in vitamin D and other micronutrient availability for a fetus, is a prevalent explanation for the variation of offspring traits with birth season. However, little consensus exists about the pregnancy period during which the fetus is most sensitive to maternal UV exposure and which offspring traits are most sensitive. We examined the association between 11 anthropometric traits and birth season/month among 18,459-23,876 Estonian children born in 1937-62. Nine traits showed seasonal patterns, which were generally weak, compared to the effects of family socioeconomic position (SEP). Most prominent nonlinear associations between offspring traits and birth month emerged among children of mothers in unskilled manual professions. A possible explanation is that the growth of children in high-SEP families is more strongly buffered against any external exposures (including possible shortage of maternally synthesised vitamin D and essential micronutrient availability) than in low-SEP settings. For most traits, children born in spring/summer were larger than those born in autumn/winter. Hip width, trunk length and weight showed the most distinct seasonal patterns. If these birth-season-related patterns are related to maternal sunlight exposure, our results support the view that UV exposure benefits offspring growth towards the end of pregnancy. It is also possible that children born in spring and summer benefitted from the seasonally increasing nutrient availability during the first post-natal months.

Antenatal steroids (ANS) are one of the most widely prescribed medications in pregnancy, being administered to women at risk of preterm delivery. In the setting of preterm delivery at or below 35 weeks' gestation, systematic review data show ANS reduce perinatal morbidity and mortality, primarily by promoting fetal lung maturation. However, with the expanding use of this intervention has come a growing appreciation for the potential off-target, adverse effects of ANS therapy on wider fetal development. We undertook a narrative literature review of the animal and clinical literature to assess current evidence for adverse effects of ANS exposure and fetal development. This review presents a summary of the evidence relating to the potential for wide-ranging, off-target, adverse effects of ANS therapy on fetal development and programming. We highlight an urgent need for further animal and clinical studies investigating the effects of ANS on the fetal immune, cardiovascular, renal and hepatic systems given a current sparsity of evidence. We also strongly suggest an emphasis on open disclosure, discussion and education of clinicians and patients with regard to the potential benefits and risks of ANS therapy, particularly in late preterm and term gestations where infants derive relatively few benefits from these drugs. We also propose further studies on the optimisation of ANS therapy through improved patient selection and improved dosing regimens based on a pharmacokinetic-pharmacodynamic informed understanding of ANS action on the fetal lung.

Obesity during development has been reported to be a determinant factor in the future development of non-communicable diseases (NCDs). Parental obesity is suggested to be a predictor of children's obesity, and it is important to consider parental factors to prevent NCDs in the progeny. Previously, we showed that paternal height had a stronger association with infant birth weight than paternal body mass index (BMI) in the Japanese population. However, only a few studies have examined the association between paternal physique and postnatal obesity. This study aimed to investigate the association between parental physique and obesity in children at the age of 3. This study used fixed data on 33,291 parent-child pairs from the Japan Environment and Children's Study, an ongoing national birth cohort study. The association between paternal physique (BMI and height) and children's obesity at the age of 3 was examined using multivariate logistic regression analysis. The higher the paternal BMI quartiles, the higher the odds ratio for obesity in male and female children at 3 years of age (P < 0.0001). However, paternal height quartiles were not associated with male or female obesity. These results differ from the association between paternal physique and infant birth weight, and it is possible that prenatal epigenetic and environmental factors of paternal origin were responsible for the differences between these two studies. The association between paternal BMI and obesity in children at the age of 3 suggests that paternal factors may be involved in the development of NCDs in future progeny.

Adverse environmental conditions during early life are known to determine adult metabolic phenotype in laboratory species and human populations. However, less is known about developmental programming of adult metabolic phenotype in livestock, given their size and longevity compared to laboratory animals. As maternal and/or fetal glucocorticoid (GC) concentrations rise in stressful conditions during pregnancy, GCs may act as a common mechanism linking early-life environmental conditions to the subsequent metabolic phenotype. This review examines prenatal and longer-term postnatal programming of metabolism by early-life GC overexposure in livestock species with a particular emphasis on sheep. It examines the effects of both cortisol, the natural glucocorticoid and more potent synthetic GCs used clinically to treat threatened pre-term delivery and other conditions during pregnancy. It considers the effects of early- life GC overexposure on the metabolism of specific feto-placental and adult tissues in relation to changes in the growth trajectory, other metabolic hormones and in the functioning of the hypothalamic-pituitary-adrenal axis itself. It highlights the role of GCs as maturational and environmental signals in programming development of a metabolic phenotype fit for survival at birth and future homeostatic challenges. However, the ensuing metabolic phenotype induced by early GC overexposure may become inappropriate for the prevailing postnatal conditions and lead to metabolic dysfunction as functional reserves decline with age. Further studies are needed in livestock to establish whether the metabolic outcomes of early-life GC overexposure are sex-linked, more pronounced in old age and inherited transgenerationally in these species.

Since the 1980s, research has linked environmental factors to adult-onset diseases. The DOHaD theory suggests that exposures during development can permanently affect organ function, predisposing individuals to adult diseases. Studies indicate that protein restriction or a high-fat diet (HFD) during this phase impacts adult metabolism since programmed dysfunctions may depend on changes established during puberty, such as the reproductive system. However, there are no studies on the impact of low-protein (LP) or HFD on male testicles during this phase. For this, Male Wistar rats were categorized into three dietary groups: LP (isocaloric low-protein pelletized); HFD; and Control (balanced commercial) until PND 60. This study was approved by the CEUA-UEM. On postnatal day 61, the animals were euthanized for histopathological, sperm count, and oxidative stress assessments in the testis and epididymis. Statistical analyses were conducted following established ethical principles in animal research. The research revealed significant alterations in daily sperm production and transit through the epididymis. Sperm morphology was affected in the experimental groups. Mitochondrial activity increased in the HFD group. Testicular and epididymal histopathology, seminiferous tubule diameter, and germinal epithelium height, as well as the number of Sertoli and Leydig cells, remained unchanged. Stereological analysis revealed tissue remodeling in the epididymis, particularly in the LP group. LP group showed an increase in lipid peroxidation in the oxidative damage test. In conclusion, low-protein and HFD during peripubertal age did not affect postnatal testicular development in rats. However, they impacted sperm quality, potentially affecting fertility and male reproductive system development.

The current study examines the application of the Pediatric-Buccal-Epigenetic (PedBE) clock, designed for buccal epithelial cells, to endothelia. We evaluate the association of PedBE epigenetic age and age acceleration estimated from human umbilical vein endothelial cells (HUVECs) with length of gestation and birthweight in a racially and ethnically diverse sample (analytic sample n = 333). PedBE age was positively associated with gestational age at birth (r = 0.22, p < .001) and infant birth weight (r = 0.20, p < .001). Multivariate models revealed infants with higher birth weight (adjusted for gestational age) had greater PedBE epigenetic age acceleration (b = 0.0002, se = 0.0007, p = 0.002), though this effect was small; findings were unchanged excluding preterm infants born before 37 weeks' gestation. In conclusion, the PedBE clock may have application to endothelial cells and provide utility as an anchoring sampling point at birth to examine epigenetic aging in infancy.

The maternal restraint stress animal model is based on a long-term stress paradigm administered to pregnant maternal animals, and these offspring have been shown to exhibit a variety of biochemical defects including obesity. This study aimed to investigate whether maternal restraint stress affects obesity-associated changes in offspring intestinal microbiota and the adipogenic differentiation of mesenchymal stem cells (MSCs).Pregnant mice were subjected to restraint stress three times daily from gestational Day12 to delivery. Changes in the composition of the intestinal microbiota of mothers (during pregnancy and lactation) and their lactating offspring exposed to maternal restraint stress were analyzed using next-generation sequencing. Maternal stress altered the maternal microbiota, with reduced Bacteroidetes and increased Firmicutes. While similar trends were observed in offspring, these changes were not statistically significant. However, maternal stress notably reduced microbial diversity in the offspring's intestinal microbiota. Bone marrow-derived MSCs from offspring at weaning were analyzed for adipogenic transcription factors and hormone receptor expression using quantitative PCR. Maternal stress enhanced the adipogenic phenotype of offspring MSCs, as evidenced by increased expression of adipogenic markers (PPARγ, leptin receptor) and a reduced osteogenic phenotype. In vitro induction further confirmed the higher adipocyte differentiation potential in stressed offspring MSCs compared to controls.Our results revealed that maternal restraint stress altered the maternal intestinal microbiota, leading to reduced microbial diversity in offspring, predisposing their MSCs toward an adipocyte phenotype. These finding suggest that modulating the intestinal microbiota of stressed pregnant women may improve the susceptibility to obesity in their children.

The incidence of congenital malformations (CM) among non-Hispanic White American (NHWA) mothers was reviewed to identify and evaluate the geographic differences in the most frequent CM subtypes associated with smoking and other risk factors. Data on CM were obtained from 150,775 children (2000-2004) from the Centers for Disease Control and Prevention. Risk factors associated with CM development were the mother's age < 21 and > 35 years, body weight gain during pregnancy, anemia, diabetes mellitus, eclampsia (cases of preeclampsia were omitted), smoking, and alcohol use during pregnancy. Among smoking mothers, the most common CM was omphalocele, club foot, cleft lip, and polydactyly. The highest incidences (CM/10,000 births/year) of observed CM in children of smoking mothers were clubfoot, 25.51 cases (Utah), cleft lip, 22.47 (South Dakota), polydactyly, 21.23 (North Dakota), and omphalocele, 13.14 (Montana). The presence of maternal comorbidities, tobacco and alcohol consumption, and their association with other environmental factors can affect the incidence of CM in NHWA mothers. Further comparisons among the American states regarding the overall changes in CM over the last two decades should uncover crucial outcomes in terms of CM and smoking.

Low birthweight is a risk factor for type 2 diabetes. We hypothesised that differential associations between birthweight and clinical characteristics in persons with and without type 2 diabetes may provide novel insights into the role of birthweight in type 2 diabetes and its progression. We analysed UK Biobank data from 9,442 persons with and 254,446 without type 2 diabetes. Associations between birthweight, clinical traits, and genetic predisposition were assessed using adjusted linear and logistic regression, comparing the lowest and highest 25% of birthweight to the middle 50%. Each kg increase in birthweight was associated with higher BMI, waist, and hip circumference, with stronger effects in persons with versus without type 2 diabetes (BMI: 0.74 [0.58, 0.90] vs. 0.21 [0.18, 0.24] kg/m²; waist: 2.15 [1.78, 2.52] vs. 1.04 [0.98, 1.09] cm; hip: 1.65 [1.33, 1.97] vs. 1.04 [1.04, 1.09] cm). Family history of diabetes was associated with higher birthweight regardless of diabetes status, albeit with a twofold higher effect estimate in type 2 diabetes. Low birthweight was further associated with prior myocardial infarction regardless of type 2 diabetes status (OR 1.33 [95% CI 1.11, 1.60] for type 2 diabetes; 1.23 [95% CI 1.13, 1.33] without), and hypertension (OR 1.25 [1.23, 1.28] and stroke 1.24 [1.14, 1.34]) only among persons without type 2 diabetes. Differential associations between birthweight and cardiometabolic traits in persons with and without type 2 diabetes illuminate potential causal inferences reflecting the roles of pre- and postnatal environmental versus genetic aetiologies and disease mechanisms.