Journal of Developmental Origins of Health and Disease最新文献

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.

This study aimed to investigate the mechanisms by which the association between maternal hyperglycemia and postnatal high-fat diet (HFD) exposure compromises metabolic parameters and hepatic autophagy in adult female pups. For this, Sprague Dawley rats, female pups from nondiabetic (control = FC) or diabetic (FD) mothers, were fed a standard diet (SD) or HFD from weaning until adulthood (n minimum = 5 rats/group): FC/SD, FC/HFD, FD/SD, and FD/HFD. In adulthood, these rats were tested with the oral glucose tolerance test, euthanized, and serum biochemistry parameters were analyzed. Liver samples were collected to evaluate cytokines, redox status, and protein expression autophagy and apoptosis markers. Histomorphometric analyses and an assessment of lipofuscin accumulation were also performed to reflect incomplete autolysosomal digestion. The FC/HFD, FD/SD, and FD/HFD groups showed glucose intolerance and an increased number of hepatocytes. Furthermore, FD/SD and FD/HFD rats showed hyperlipidemia and insulin resistance. Adaptations in hepatic redox pathways were observed in the FD/SD group with increased antioxidant defense marker activity. The FD/SD group also exhibited increased autophagy protein expression, such as p-AMPK, LC3-II/LC3-I, and p62/SQSTM1, lipofuscin accumulation, and caspase-3 activation. After exposure to HFD, the adult female pups of diabetic rats had a reduced p-AMPK and LC3-II/LC3-I ratio, the presence of steatosis, oxidative stress, and inflammation. The reduction of autophagy, stimulated by HFD, may be of vital importance for the susceptibility to metabolic dysfunction-associated fatty liver disease induced by maternal diabetes.

Long-term birth cohorts are essential for studying health and disease over the life course. The retention of participants remains a challenge in study design. Previous research works on attrition are limited in length of follow-up time and lack of racial/ethnic diversity. Using data from the Wayne County Health, Environment, Allergy, and Asthma Longitudinal Study (WHEALS; United States cohort born between 2004 and 2007, n = 1258), we first performed longitudinal latent class analyses to identify patterns of participation spanning the prenatal period and six follow-up timepoints: 1, 6, 12, and 24 months; 3-6 years; and 10-12 years. Data collection included a combination of in-person visits, home visits, home specimen kits, and staff-administered questionnaires. We examined associations between baseline factors and participation class using multinomial logistic regression modeling, and with conditional inference modeling to identify variables most strongly associated with class. We identified four participation classes: high early participation with gradual loss-to-follow-up, sporadic participation, consistently high participation, and consistently low participation. Multiple baseline characteristics were associated with participation class. The "consistently high participation" class was disproportionately composed of participants who were older, were of higher education, had private insurance, had suburban residence, and were with higher income. Conditional inference trees identified maternal education, insurance, and income as most strongly associated with participation class. Through latent class modeling, we show that participants who were lost to follow-up fell into distinct groupings of participation. In the future, preparatory communications with those who are at the highest risk of study discontinuation may improve long-term retention.

In 2024, we are celebrating the 280th anniversary of Jean-Baptiste Lamarck, whose early theories on inheritance and environmental adaptation have advanced the foundational concepts of Developmental Origins of Health and Disease (DOHaD). This proposal aims to explore how some Lamarckian ideas align with contemporary understandings of how environmental factors in early life can affect health throughout an individual's lifetime and across generations. This text not only honors an important historical milestone but also reflects on how a DOHaD notion might have been present since the earliest years of biological science. It bridges historical scientific thought with present-day scientific research.

In utero exposure to income shocks has a lasting effect on child well-being. In an agricultural economy, fluctuations in rainfall directly affect household income. In this paper, we investigate the short- and long-run impact of pre-pregnancy, prenatal, and early-life exposure to fluctuations in rainfall on height for a sample of 2290 children in rural Pakistan. Given the widespread canal irrigation system prevalent in the country, we also investigate how fluctuations in river water flows affect child health. We find that fluctuations in rainfall during the pre-pregnancy period have the most lasting effects on the stature of children in the short and long run. Exposure of a mother to a 1 standard deviation reduction in rainfall during the pre-pregnancy period led her child to be 0.17 standard deviations (0.53 cm) shorter by age four. This negative impact of a pre-pregnancy rainfall shock on height persisted over time; the child continued to be 0.12 standard deviations (0.83 cm) shorter, on average, by 13 years of age. However, we find that the effect of pre-pregnancy rainfall fluctuations on children's height is smaller in districts that have access to irrigation facilities.

Breast milk (BM) is the only source of iodine and bioactive compounds that influence growth and development in infants. The content of BM may be influenced by maternal body mass index (BMI). The aim of this study was to investigate the effect of maternal weight on BM and cord blood iodine concentrations, growth-related hormones, infant anthropometric measurements. A total of 84 mother-infant pairs participated. Levels of leptin, adiponectin and insulin-like growth factor-I (IGF-I) in postnatal BM and cord blood were analysed by enzyme-linked immunosorbent assay (ELISA), iodine by Sandell-Kolthoff reaction. Dietary iodine intake of women was determined by food frequency questionnaire, and anthropometric measurements of infants at birth and 3 months were evaluated. Dietary iodine intake was found to be similar in normal weight (NW) and overweight/obese (OW/OB) women (p > 0.05). Breast milk iodine concentration (BMIC) was 17.4 μg in NW, 18.2 μg in OB/OW women. Adiponectin in cord blood and IGF-I in BM were higher OB/OW than NW women (p < 0.05). Positive correlations were found between the infant birth weight and adiponectin in BM, between the infant body weight at 3 months and leptin and adiponectin in BM, between the infant birth head circumference and IGF-I in BM (p < 0.05). In multiple linear regression model, leptin and adiponectin in BM had a positive effect on infant body weight (p < 0.05). Maternal BMI may influence infant body weight via leptin and adiponectin in BM and infant head circumference via IGF-I. No relationship was found between maternal BMI and iodine levels and anthropometric measurements of the infant. Longitudinal studies are recommended to understand the effect of BMIC on growth.