257: The added value of whole exome sequencing (WES) in fetuses with structural abnormalities (original) (raw)
Related papers
255: The hepatic circadian gene npas2 regulates satiety and obesity in response to a high-fat diet
American Journal of Obstetrics and Gynecology
SGA (42.9 vs. 30.0%). However, 95% confidence intervals overlapped (Table 1). Specificity between NICHD and Hadlock were similar. Both charts similarly identified low numbers of fetuses who subsequently were admitted to the NICU, had pH less than 7.2 or 5 minute Apgar of less than 7. When FGR was defined at less than 10th%, the sensitivity to detect an FGR fetus who subsequently developed SGA was similar among NICHD and Hadlock standards. NICU admissions, pH of less than 7.2 and 5 minute Agpar of less than 7 were also similar among groups when FGR was defined at less than 10th%. CONCLUSION: Although the Hadlock's chart appears to diagnose more cases of neonatal SGA, short-term outcomes appear similar to the NICHD standard. Differences in long-term outcomes between standards are unknown.
American Journal of Obstetrics and Gynecology, 2011
Fetal congenital heart disease may lead to abnormal fetal growth. Our objective was to characterize the association between all fetal congenital heart disease (CHD) and intrauterine growth restriction (IUGR). STUDY DESIGN: In a retrospective cohort study, we collected outcome data from singleton pregnancies undergoing routine anatomic survey at a tertiary medical center between 1990 and 2008. A dedicated research nurse collected information on delivery outcomes prospectively. Subjects with a prenatal diagnosis of fetal CHD were compared to those without CHD. Stratified analyses for isolated fetal CHD and major CHD were performed. The primary outcome was IUGR less than 10th percentile. Logistic regression was used to adjust for confounding variables and refine the estimates of risk. RESULTS: Among 66,956 patients, there were 175 cases of fetal CHD (0.26%) and 5,192 cases of IUGR (8.4%). Prenatal diagnosis of CHD was associated with an increased risk of IUGR, and the risk was greatest in fetuses with major CHD (Table 1). Isolated CHD was also associated with an increased risk of IUGR (Table 1). CONCLUSIONS: Compared to controls, patients with a prenatal diagnosis of fetal CHD are twice as likely to develop IUGR, even after excluding extracardiac and karyotypic anomalies. Based on our findings, serial growth assessment may be a reasonable option for patients with fetal CHD diagnosed at routine anatomic survey.
Brain Research, 2008
Human and animal studies suggest that obesity in adulthood may have its origins partly during prenatal development. One of the underlying causes of obesity is the perturbation of hypothalamic mechanisms controlling appetite. We determined mRNA levels of genes that regulate appetite, namely neuropeptide Y (NPY), pro-opiomelanocortin (POMC) and the leptin receptor isoform Ob-Rb, in the hypothalamus of adult mouse offspring from pregnant dams fed a protein-restricted diet, and examined whether mismatched post-weaning highfat diet altered further expression of these gene transcripts. Pregnant MF1 mice were fed either normal protein (C, 18% casein) or protein-restricted (PR, 9% casein) diet throughout pregnancy. Weaned offspring were fed to adulthood a high-fat (HF; 45% kcal fat) or standard chow (21% kcal fat) diet to generate the C/HF, C/C, PR/HF and PR/C groups. Food intake and body weight were monitored during this period. Hypothalamic tissues were collected at 16 weeks of age for analysis of gene expression by real time RT-PCR. All HF-fed offspring were observed to be heavier vs. C groups regardless of the maternal diet during pregnancy.
Molecular Metabolism, 2021
Childhood obesity is a strong risk factor for adult obesity, type 2 diabetes, and cardiovascular disease. The mechanisms that link early adiposity with late-onset chronic diseases are poorly characterised. We developed a mouse model of early adiposity through litter size reduction. Mice reared in small litters (SLs) developed obesity, insulin resistance, and hepatic steatosis during adulthood. The liver played a major role in the development of the disease. Objective: To gain insight into the molecular mechanisms that link early development and childhood obesity with adult hepatic steatosis and insulin resistance. Methods: We analysed the hepatic transcriptome (Affymetrix) of control and SL mice to uncover potential pathways involved in the long-term programming of disease in our model. Results: The circadian rhythm was the most significantly deregulated Gene Ontology term in the liver of adult SL mice. Several core clock genes, such as period 1e3 and cryptochrome 1e2, were altered in two-week-old SL mice and remained altered throughout their life course until they reached 4e6 months of age. Defective circadian rhythm was restricted to the periphery since the expression of clock genes in the hypothalamus, the central pacemaker, was normal. The period-cryptochrome genes were primarily entrained by dietary signals. Hence, restricting food availability during the light cycle only uncoupled the central rhythm from the peripheral and completely normalised hepatic triglyceride content in adult SL mice. This effect was accompanied by better realignment of the hepatic period genes, suggesting that they might have played a causal role in mediating hepatic steatosis in the adult SL mice. Functional downregulation of Per2 in hepatocytes in vitro confirmed that the period genes regulated lipid-related genes in part through peroxisome proliferator-activated receptor alpha (Ppara). Conclusions: The hepatic circadian rhythm matures during early development, from birth to postnatal day 30. Hence, nutritional challenges during early life may misalign the hepatic circadian rhythm and secondarily lead to metabolic derangements. Specific time-restricted feeding interventions improve metabolic health in the context of childhood obesity by partially realigning the peripheral circadian rhythm.
American journal of obstetrics and gynecology, 2017
We have recently shown in both non-human primates and in rodents that fetal and neonatal hepatic expression of the circadian transcription factor, Npas2, is modulated by a high fat maternal diet and plays a critical role in establishing life-long metabolic homeostasis. Similarly, we and others have also established the importance of the maternal and early postnatal diet on establishment of the early gut microbiome. We hypothesized that altered circadian gene expression solely in the neonatal liver would result in gut microbiome dysbiosis, especially with diet-induced metabolic stress (ie, restricted feeding). Using a murine model in which we conditionally knock out Npas2 in the neonatal liver, we aimed to determine the role of the circadian machinery in gut dysbiosis with restricted feeding. We collected fecal samples from liver Npas2 conditional knockout (n = 11) and wild-type (n = 13) reproductive-aged mice before (study day 0) and after the restricted feeding study (study day 17)...
PLoS One, 2009
A link has been established between prenatal nutrition and the development of metabolic and cardiovascular diseases later in life, a process referred to as developmental programming. It has been suggested that the trajectory of development is shifted by alterations in the maternal nutritional state leading to changes in developmental plasticity, in part underpinned by epigenetic changes in gene regulation. However, to date, only candidate gene approaches have been used to assess expression and molecular changes in the offspring of maternally undernourished animals. Furthermore, most work has focused on animals at an age where the programmed phenotype is already manifest and little is known about changes in gene expression in the offspring prior to development of obesity and related metabolic disorders. Gene expression profiles of liver, retroperitoneal white adipose fat, and biceps femoris skeletal muscle tissue from young adult male rats (55 days old) in which nutritional status had been manipulated in utero by maternal undernutrition (UN) were compared to the profiles of offspring of ad libitum fed mothers serving as the control group (AD) (8 offspring/group). The expression profiles were determined using the Illumina RatRef-12 BeadChip. No significant changes in expression were identified for skeletal muscle or white adipose tissue. However, studies of liver tissue showed 249 differentially expressed genes (143 up regulated, 106 down regulated). Although the animals at day 55 have yet to develop obesity they already show biochemical abnormalities and by day 110 express a phenotype characterized by increased adiposity and altered insulin sensitivity. An analysis of pathways affected suggests that intrauterine programming of UN animals to favor fat as an energy source results in mitochondrial dysfunction which initially affects the postnatal hepatic function and subsequently, via the resultant metabolic changes in other organs leads to the evolution of a phenotype similar to that of the metabolic syndrome.
Nutrients
Obesogenic environments such as Westernized diets, overnutrition, and exposure to glycation during gestation and lactation can alter peripheral neuroendocrine factors in offspring, predisposing for metabolic diseases in adulthood. Thus, we hypothesized that exposure to obesogenic environments during the perinatal period reprograms offspring energy balance mechanisms. Four rat obesogenic models were studied: maternal diet-induced obesity (DIO); early-life obesity induced by postnatal overfeeding; maternal glycation; and postnatal overfeeding combined with maternal glycation. Metabolic parameters, energy expenditure, and storage pathways in visceral adipose tissue (VAT) and the liver were analyzed. Maternal DIO increased VAT lipogenic [NPY receptor-1 (NPY1R), NPY receptor-2 (NPY2R), and ghrelin receptor], but also lipolytic/catabolic mechanisms [dopamine-1 receptor (D1R) and p-AMP-activated protein kinase (AMPK)] in male offspring, while reducing NPY1R in females. Postnatally overfed ...
Differential Effects of Post-Weaning Diet and Maternal Obesity on Mouse Liver and Brain Metabolomes
Nutrients
Nutritional changes during developmental windows are of particular concern in offspring metabolic disease. Questions are emerging concerning the role of maternal weight changes before conception, particularly for weight loss, in the development of diet-related disorders. Understanding the physiological pathways affected by the maternal trajectories in the offspring is therefore essential, but a broad overview is still lacking. We recently reported both metabolic and behavioral negative outcomes in offspring born to obese or weight-loss mothers and fed a control of high-fat diet, suggesting long-term modeling of metabolic pathways needing to be further characterized. Using non-targeted LC–HRMS, we investigated the impact of maternal and post-weaning metabolic status on the adult male offspring’s metabolome in three tissues involved in energy homeostasis: liver, hypothalamus and olfactory bulb. We showed that post-weaning diet interfered with the abundance of several metabolites, incl...
British Journal of Nutrition, 2008
Both in man and in animal models, changes in food intake and body composition in later life have been reported after alterations in perinatal nutrition. Therefore, we hypothesised that early postnatal undernutrition in the rat induces permanent changes in energy balance. Food restriction (FR) during lactation was achieved by enlarging litter size to twenty pups, whereas control animals were raised in litters containing ten pups. Energy intake and resting energy expenditure were determined in adult males. Early postnatal FR resulted in acute growth restriction followed by incomplete catch-up in body weight, body length and BMI. At the age of 12 months, middle-aged FR males had significantly lower absolute resting energy expenditure (200 v. 216 kJ/24 h, P¼ 0·009), absolute energy intake (281 v. 310 kJ/24 h, P¼ 0·001) and energy intake adjusted for BMI (284 v. 305 kJ/24 h, P¼ 0·016) than controls, whereas resting energy expenditure adjusted for BMI did not differ significantly between the groups (204 v. 211 kJ/24 h, P¼ 0·156). The amount of energy remaining for other functions was lower in FR males (80 v. 94 kJ/24 h, P¼ 0·044). Comparable data were obtained at the age of 6 months. These results indicate that in rats energy balance can be programmed by early nutrition. A low early postnatal food intake appears to programme these animals for a low energy intake and to remain slender in adult life.
Nutrients, 2021
Background: Time restricted feeding (TRF) refers to dietary interventions in which food access is limited during a specific timeframe of the day. TRFs have proven useful in improving metabolic health in adult subjects with obesity. Their beneficial effects are mediated, in part, through modulating the circadian rhythm. Nevertheless, the translation of these dietary interventions onto obese/overweight children and adolescents remains uncharacterized. The objective of this study is to explore the feasibility of temporal dietary interventions for improving metabolic health in the context of childhood obesity. Methods: We have previously developed a mouse model of early adiposity (i.e., childhood obesity) through litter size reduction. Mice raised in small litters (SL) became obese as early as by two weeks of age, and as adults, they developed several obesity-related co-morbidities, including insulin resistance, glucose intolerance and hepatic steatosis. Here, we explored whether two in...