Journal of Developmental Origins of Health and Disease最新文献

Cyantraniliprole is a widely used insecticide that disrupts calcium homeostasis by binding to ryanodine receptors (RyRs) in the sarcoplasmic reticulum. Insects have a type of RyR with a 47% sequence homology to mammalian RyRs. Due to the high homology and strong affinity of cyantraniliprole for insect RyRs, concerns have been raised about potential adverse effects in mammals. This study aimed to evaluate the effects of cyantraniliprole on the liver and kidneys of male Wistar rat offspring exposed to a dose of 10 mg/kg during gestation and lactation. Thirty-three 80-day-old pregnant Wistar rats were randomly assigned to either a control group or a cyantraniliprole group (10 mg/kg). The treatment period lasted from the 5th gestational day to the 21st lactational day. The offspring were euthanized on postnatal day 55 (puberty) or 90 (adulthood). Blood samples were collected for biochemical assays, and liver and kidney samples were collected for histopathological analysis, oxidative stress biomarkers, and inflammatory profile assessment. The results indicated that exposure to cyantraniliprole caused vacuolation and vascular congestion in the pubertal and adult offspring, as well as significant morphological changes in the liver and kidneys. There was an increase in catalase and glutathione S-transferase activity in response to oxidative stress induced by the insecticide in the liver, with elevated levels of thiobarbituric acid reactive substances in the liver of adult animals and increased myeloperoxidase activity in pubertal animals. These findings suggest that exposure to cyantraniliprole induces significant damage to the organs involved in metabolism and excretion.

Neonatal growth assessment during the first 28 days of life is a critical determinant of infant health and survival. Anthropometric measurements provide a simple, inexpensive, and non-invasive means to evaluate neonatal size, nutritional status, and growth, as well as to predict long-term health outcomes. Alongside standard growth curves, methods for assessing neonatal body composition offer additional insights into fat and fat-free mass distribution, which are linked to later risks such as childhood obesity and metabolic complications. This review summarizes the commonly used anthropometric measures and advanced laboratory techniques for assessing neonatal growth and body composition, discusses their advantages and limitations, and highlights the importance of their combined use in clinical and research settings. Understanding these methods is essential for early identification of growth disturbances and for promoting optimal nutrition and health outcomes throughout the life course.

Maternal consumption of a high-fat diet (mHFD) during perinatal life influences hypothalamic-pituitary-adrenal (HPA) axis activation and impacts the long-term physiological and metabolic health of offspring. Milk-derived extracellular vesicles (MEVs) are lipid-coated nanovesicles that transfer biological materials from mother to infant and can survive intestinal degradation and cross the blood-brain barrier. MEVs provide cytoprotection in peripheral organs; however, their pro-survival functions remain unknown in the neonatal brain. Further, sex differences resulting from MEV treatment require investigation, as male and female neonates display variable responses to early life nutrient stress. We investigated the interaction between MEVs and the heat shock protein response in the liver, hypothalamus, and prefrontal cortex in male and female neonatal rats exposed to perinatal mHFD at postnatal day 11. MEV treatment robustly modulated the HSR in female neonates with the largest response recorded in the prefrontal cortex. These results suggest that MEVs may influence pro-survival outcomes in the prefrontal cortex by activating HSF1-mediated pro-survival in a sex-specific manner.

Hormone exposure in utero affects male- and female-typical behavior in animals, and these effects may persist in the next generation. Prenatal exposure to diethylstilbestrol (DES), a potent estrogen and endocrine disruptor, has been associated with a tendency toward greater heterosexual behavior in women, but the association in the next generation has not been studied. We evaluated the associations of maternal prenatal DES exposure with sexual behavior, sexual identity, and gender identity in 982 female offspring participating in the National Cancer Institute's DES Third Generation Study, a cohort born to mothers who were prenatally exposed and unexposed to DES. Odds ratio (OR) and 95% confidence intervals (CIs) were estimated from logistic regression models that included birth year. The ORs were 0.71 (CI 0.46-1.1) for DES in relation to non-heterosexual compared with heterosexual behavior, and 0.99 (CI 0.55-1.8) for non-heterosexual identity, compared with heterosexual identity. Results were similar after additional adjustment for education. Only three individuals reported a gender identity distinct from what was reported by the mother at cohort inception, preventing meaningful quantitative analysis of DES and gender identity. These data do not provide evidence of differences in sexual behavior and sexual identity in female offspring of mothers with and without prenatal exposure to DES.

Early life, or the neonatal period, is perhaps the most challenging time for ruminant livestock, as they adapt to the extra-uterine environment, undergo important physiological maturation, and navigate harsh ambient conditions. Maternal influences during gestation, especially energy and protein nutrition in late pregnancy, can alter many processes that affect the neonatal period. These processes include fetal growth and development, gestation length, difficulty of parturition, and maternal behavior, which interact to affect offspring vigor at birth. Moreover, colostrum and early milk production and composition are affected by gestational nutrition, and these along with the previous factors affect the neonate's ability to obtain transfer of passive immunity, thermoregulate, perform basal metabolism, and ultimately survive to weaning. Often, the long-term effects of maternal nutrition during gestation on offspring are attributed solely to the prenatal environment, but it is critical to also consider influences of early life on later productivity and health. More research is needed to integrate these neonatal outcomes with prenatal and postnatal mechanisms as well as later ruminant livestock performance. Better understanding of the maternal environment's effects on the neonatal period provides opportunity for improved management of ruminant livestock dams and offspring.

The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) has increased. MASLD notably increases after menopause in women owing to the drastic reduction in estrogen, which regulates lipid metabolism. While prenatal undernutrition leads to hepatic steatosis after birth, whether prenatal undernutrition affects the onset of postmenopausal MASLD remains unknown. Therefore, we examined the impact of early prenatal undernutrition on the predisposition to postmenopausal MASLD in a rat model of menopause. Pregnant female rats were assigned to the control (CNTL) group, while the undernourished (UN) group was fed 40% of the diet of the control group. Furthermore, both groups were assigned to the ovariectomized (CNTL-OVX/UN-OVX) and sham-operated (CNTL-Sham/UN-Sham) groups at 12 weeks of age. Two-way analysis of variance revealed significant main effects of ovariectomy and prenatal undernutrition on body weight and hepatic triglyceride content. Triglycerides accumulated in the liver at 12 and 24 weeks after ovariectomy, while hepatic steatosis was histologically observed at 24 weeks after ovariectomy in UN-OVX rats. Hepatic gene expression analyses showed an interaction effect between prenatal undernutrition × ovariectomy in ESR1 expression; however, PPARα, RXRα, RARα, Raldh1, and Raldh3 expression was not affected by prenatal undernutrition and ovariectomy. These results suggest that early prenatal undernutrition predisposes postmenopausal women to MASLD by uncovering aberrant estrogen signaling, which may be influenced by estrogen reduction.

The impact of maternal nutrition during the peri-conception period on offspring sex remains unclear. Therefore, this study aimed to explore the association between maternal nutritional intake around conception and offspring sex. Data were collected from the Japan Environment and Children's Study, which enrolled 97,510 mother-child pairs. The effect of maternal intake of fats, proteins, and fatty acids on offspring sex was analyzed, adjusting for maternal demographics and lifestyle factors. Overall, maternal intake of total fatty acids, saturated fatty acids (SFAs), polyunsaturated fatty acids (PUFAs), n-3 PUFA, n-6 PUFA, and protein and the ratios of n-6/n-3 and SFA/energy showed no consistent associations with offspring sex.However, further analyses revealed notable patterns related to maternal age and energy intake. Among mothers with high energy intake (≥4,000 kcal/day), higher residual protein intake was associated with increased odds of having a male child (aOR, 1.87; 95% CI, 1.17-2.98). In mothers aged under 20 years, increased n-3 PUFA intake was linked to higher odds of male births, while a higher n-6/n-3 ratio was associated with lower odds of male births. Additionally, among mothers aged 20-35 years, higher n-3 PUFA intake was associated with decreased odds of having a male child (aOR, 0.89; 95% CI, 0.82-0.98).These findings indicate that while no consistent overall relationship was observed, certain maternal nutritional patterns may influence offspring sex, highlighting the need for further research on maternal diet and reproductive outcomes.

Iron deficiency anemia is a major health problem worldwide. Iron is an essential micronutrient in the human body; its demand increases with fetal growth and gestation. Although it has been reported that glucose metabolism is also affected by iron deficiency, only few studies have investigated the influence of iron deficiency during gestation and in offspring. In this study, glucose metabolism in newborns was investigated in terms of maternal iron deficiency prior to pregnancy in a rat model. Briefly, rats were divided into control (CL) and iron deficiency (ID) groups. The levels of serum glucose and insulin and the protein expression of liver GLUT2 in neonates born to dams in the ID group increased. In contrast, the mRNA and protein expression levels of GLUT2 and GLUT4 in the skeletal muscle tended to decrease. In addition, the expression of p-Akt (Thr308), which is involved in GLUT4 membrane translocation, decreased, suggesting that GLUT4 translocation to the plasma membrane may not have been sufficiently promoted. These results suggest that maternal iron deficiency may influence glucose metabolism in neonates and potentially increase the risk of developing metabolic abnormalities and lifestyle-related diseases later in life.

Adverse prenatal conditions can induce intrauterine growth restriction (IUGR) and increase the risk of adulthood metabolic disease. Mechanisms underlying developmentally programmed metabolic disease remain unclear but may involve disrupted postnatal circadian rhythms and kisspeptin signalling. We investigated the impact of maternal hypoxia-induced IUGR on hypothalamic and hepatic expression of clock genes (Bmal1, Per2 and Reverbα), metabolic genes (Pparα, Pparγ and Pgc1α) and kisspeptin genes (Kiss1 and Kiss1r) in adult offspring. Pregnant BALB/c mice were housed in hypoxic conditions (10.5% oxygen) from gestational day 11 to 17.5 and then returned to normoxic conditions until term (gestational day ∼ 21). Control animals were housed in normoxic conditions throughout pregnancy. Offspring were weighed at birth. At 8 weeks of age, body, liver and brain tissues were collected and weighed. Relative clock gene, metabolic gene and kisspeptin signalling gene expression were measured using qPCR. The IUGR offspring were lighter at birth and remained lighter at 8 weeks but with higher brain relative to body weight. The IUGR offspring had decreased hypothalamic Bmal1 and Reverbα expression, but unchanged hepatic clock gene expression and no change in hypothalamic or hepatic Per2 expression, compared with Control offspring. This tissue-specific change in clock gene expression suggests circadian dysregulation. There were no IUGR-related changes to metabolic gene expression in the hypothalamus or liver, but IUGR offspring had increased hypothalamic Kiss1r expression. These results demonstrate IUGR offspring from hypoxia pregnancies show central circadian misalignment and potentially disrupted hypothalamic Kiss1/Kiss1r signalling, which may contribute to developmentally programmed metabolic disease.

This study aimed to investigate the effects of infant formula supplements on Bifidobacterium level in the infant gut through a systematic review and network meta-analysis (NMA) of randomized controlled trials (RCTs).Systematic review included PubMed, EMBASE, MEDLINE, Scopus, Web of Science, and Cochrane CENTRAL to identify RCTs evaluating the effects of formulas supplemented with prebiotics, probiotics, synbiotics, β-palmitic acid, or combinations of β-palmitic acid with prebiotics on infant gut Bifidobacterium levels. A meta-analysis compared bifidogenic effects to standard formula. The main outcome was the relative abundance (RA) of Bifidobacterium in fecal samples measured by various microbiota assessment techniques, with effect sizes as mean differences and standard deviations. An overall effect estimate was derived using a random-effects model. NMA assessed formula effects using breastfeeding as the reference.Nineteen studies were included. Compared to standard formula, supplementation with prebiotics (p < 0.0001), synbiotics (p < 0.0001), β-palmitic acid (p = 0.0005), or β-palmitic acid combined with prebiotics (p < 0.0001) significantly increased Bifidobacterium levels in the infant gut. Probiotic supplementation showed no significant effect (p = 0.9755). NMA and p-score ranking, comparing formulas to breastmilk, indicated that prebiotic-supplemented formulas with the lowest ranking p-score (0.2764), most closely resembled breastfeeding's bifidogenic effect. However, prebiotics and probiotics were analyzed as broad categories, and group variability may affect outcomes. In conclusion, formula supplementation with prebiotics, synbiotics, β-palmitic acid, or combinations of β-palmitic acid with prebiotics increased the RA of Bifidobacterium in infant's gut, with prebiotic formula most closely mimicking the bifidogenic effects of breastfeeding.