SPAG7 deletion causes intrauterine growth restriction, resulting in adulthood obesity and metabolic dysfunction
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ABSTRACT:
PROVIDER: PRJNA1032923 | ENA |
REPOSITORIES: ENA
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Project description:From a forward mutagenetic screen to discover mutations associated with obesity, we identified mutations in the spag7 gene linked to metabolic dysfunction in mice. Here we show that SPAG7 KO mice are born smaller and develop obesity and glucose intolerance in adulthood. This obesity does not stem from hyperphagia, but a decrease in energy expenditure. The KO animals also display reduced exercise tolerance and muscle function due to impaired mitochondrial function. Furthermore, SPAG7-deficiency in developing embryos leads to intrauterine growth restriction, brought on by placental insufficiency, likely due to abnormal development of the placental junctional zone. This insufficiency leads to loss of SPAG7-deficient fetuses in utero and reduced birth weights of those that survive. We hypothesize that a “thrifty phenotype” is ingrained in SPAG7 KO animals during development that leads to adult obesity. Collectively, these results indicate that SPAG7 is essential for embryonic development and energy homeostasis later in life.
2023-11-01 | GSE246428 | GEO
Project description:Transcriptome analyses reveal metabolic syndrome of adulthood with intrauterine growth restriction in a pig model
| PRJNA417068 | ENA
Project description:The placental transcriptome in late gestational hypoxia resulting in murine intrauterine growth restriction predicts adult cardiometabolic disease
| PRJNA448908 | ENA
Project description:Intrauterine growth restriction (IUGR) impairs fetal growth and development, perturbs nutrient metabolism, and increases the risk of developing diseases in the postnatal life. However, the underlying mechanisms by which IUGR affects fetuses remain incompletely understood. Here, we applied high-throughput proteomics approach and biochemical analysis to investigate the impact of IUGR on fetal liver.
2016-03-15 | PXD003524 | Pride
Project description:In our mouse model of intrauterine growth restriction (IUGR), we have discovered that IUGR promotes embyronic Sox2+ neural stem cell depletion as well as premature neurogenesis. Using RNA-seq, we strived to determine the differentially expressed molecular genes/pathways that may be responsible for such cellular differences between appropriately-grown and IUGR mouse offspring.
2021-09-15 | GSE173845 | GEO
Project description:<p>Intrauterine growth restriction (IUGR) is associated with increased relative liver weight at birth, hepatic function decline and a higher risk for chronic liver and cardiovascular diseases in adults. Precise mechanisms of early developmental plasticity to intervene in poor fetal programming and adult disease remain largely elusive and warrant extensive research. Selecting natural piglets’ model of IUGR, using the liver as a readout and combining previous transcriptome findings, a map of cellular landscape was created to reveal a sex-dependent manner in IUGR-induced hepatic injury and its long-term functional repercussions. At the one-week postnatal node, we reveal that in contrast to a converting trend about an immune-adapted phenotype in female IUGRs, the more severe hepatic injury in male IUGRs is attributed to persistent inflammation caused by abnormal lipid metabolism, which disrupts the interactions of non-immune cells, resulting in impaired liver regeneration lasting into adulthood. In addition, we consider APOA4 as a new biomarker for the detection of IUGRs and discover its underlying role in hypoxic conditions. Our study opens the possibility to early therapy and screening of gender-specific hepatic injury brought on by IUGR.</p>
2023-09-25 | MTBLS6881 | MetaboLights
Project description:Epidemiological data indicated intrauterine growth retardation (IUGR) is a risk factors for adult metabolic syndrome. However, the genetic mechanism underlying the phenotype in adulthood is not well characterized. Here, the present study employed adult normal and IUGR pigs as models to survey the difference of global gene expression in the liver using transcriptome sequence. The trancriptome libraries generated 104.54 gigabases data, 16,948 and 17,078 genes were expressed in normal and IUGR pigs, repectively. A total of 1,322 differentially expreesion genes (DGEs) were identified. An enrichment analysis of DGEs presented the top overrepresented GO terms and pathway were related to oxidoreductase activity, ATPase activity, amino catabolic process, glucose metabolism and Insulin signaling pathway. Finally, combined their phenotypes and gene expression patterns, we proved the adult IUGR pigs would obstruct the process of mitochondrial biogenesis and oxidative phosphorylation, which induced high oxidation press in adult IUGR. The increased gluconeogenic and decreased glycogen synthesis in liver resulted in reducing the capacity of glucose intolerance in IUGR. The decreased expression of insulin signaling genes (such as PI3K and AKT) implied a risk of diabetes in adult IUGR. Moreover, the capacity of fatty acid oxidation decreased in IUGR liver leaded to high content of triglyceride and free fatty acid in IUGR. Together, these findings provide a comprehensive understanding of the molecular mechanisms of adult IUGR pigs and valuable information for future studies of therapeutic intervention in IUGR metabolic syndrome.
2017-11-04 | GSE106512 | GEO
Project description:In this study, we profiled the placental proteome of IUGR twins and normal cotwins from 6 monochorionic twin pairs with selective intrauterine growth restriction (sIUGR).
2022-07-15 | PXD035369 |
Project description:Intrauterine growth restriction (IUGR) affects up to 10% of pregnancies and often results in short- and long- term sequelae for offspring, including risk for adult cardiovascular disease (CVD). The mechanisms underlying IUGR are poorly understood, though poor blood flow and oxygen/nutrient provision to the IUGR fetus are thought to be the common endpoints of disease. Though several animal models of IUGR exist, few demonstrate later phenotypes of CVD despite a large body of evidence in humans linking IUGR and adult CVD onset. We thus hypothesized that in murine pregnancy, maternal late gestational hypoxia (LG-H) exposure resulting in IUGR would result in (1) adult phenotypes of CVD in hypoxia-exposed offspring, and (2) the placental transcriptome will demonstrate alterations that can be linked to risk of later disease. After subjecting pregnant mice to hypoxia (10.5% oxygen) from gestational day (GD) 14.5 to 18.5, we collected placentas at GD19. We examined RNA isolated from these placentas to perform RNA sequencing and analysis. Functional gene and cluster-based analysis suggest multiple changes in structural and functional genes important for placental health, with the top dysregulation involving vascular and metabolic pathways. Concordantly, a ~ 10% decrease in birthweights and ~30% decrease in litter size after LG-H (p<0.05) was observed, suggesting an environment of placental insufficiency. We also found that offspring exposed in-utero to LG-H exhibit CVD at 4 months of age, with males being worse than females, supporting developmental programming. Specifically, males exhibit increased body weight and an enlarged heart size, whereas both males and females develop hypertension, elevated abdominal fat, elevated leptin and elevated total cholesterol levels with aging. In summary, LG-H exposure in the pregnant mouse mimics human placental insufficiency related IUGR. The placentas of these exposed fetuses demonstrate a transcriptional response to the stressor of gestational hypoxia and predicts cardiovascular and metabolic effects that culminate into hypertension and adiposity with dyslipidemia.
2019-02-13 | GSE112755 | GEO
Project description:Perturbations of the intrauterine environment can affect fetal development during critical periods of plasticity, and can increase susceptibility to a number of age-related diseases (e.g. type 2 diabetes mellitus; T2DM), manifesting sometimes decades later. We hypothesized that this biological memory is mediated by permanent alterations of the epigenome in stem cell populations. Our studies focused specifically on DNA methylation in CD34+ hematopoietic stem and progenitor cells from cord blood, and utilized a two-stage design involving genome-wide discovery followed by quantitative, single-locus validation. We found that changes in cytosine methylation occur in response to intrauterine growth restriction (IUGR), but that they are of a substantially lesser degree and involve many fewer loci than the epigenomic dysregulation observed in cancer. This is consistent with a comparable study of individuals born following maternal starvation during the Dutch famine. We also identify specific loci that are targeted for dysregulation of DNA methylation, in particular the hepatocyte nuclear factor 4α (HNF4A) gene, a well-known diabetes candidate gene not previously associated with growth restriction in utero, and other loci encoding HNF4A-interacting proteins. Our results give some insights into the potential contribution of epigenomic dysregulation in mediating the long-term consequences of IUGR, and demonstrate the value of this approach to studies of the fetal origin of adult disease. Direct comparison of DNA methylation in 10 neonatal CD34+ samples isolated from umbilical cord blood belonging to two groups: IUGR (n=5) and their age-matched controls (n=5). Each microarray consists of a two-color comparison of a methylation-sensitive representation of the genome (HpaII) with an internal methylation-insensitive control/reference (MspI).
2010-02-17 | E-GEOD-17727 | biostudies-arrayexpress