Severe damage on placental fetal capillary network causes mid to late fetal lethality and reduction of placental size in Peg11/Rtl1 KO mice
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PROVIDER: PRJNA349026 | ENA |
REPOSITORIES: ENA
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Project description:Paternally expressed 11/Retrotransposon-like 1 (Peg11/Rtl1) knockout (KO) mice exhibited mid to late fetal lethality or late fetal growth retardation associated with frequent neonatal lethality. The lethal phenotype was largely dependent on genetic background and became more severe with each succeeding generation in the course of backcross experiments to C57BL/6 (B6). We previously suggested these lethal and growth phenotypes were due to severe defects in placental fetal capillaries in labyrinth layer. In this study, we reexamined KO fetuses exhibiting mid fetal lethality with internal bleeding. Importantly, basal region of fetal capillary network was specially damaged, therefore, also leading to poor expansion of the labyrinth layer and placental size reduction in later stage. Apparent up-regulation of Guanine nucleotide binding protein, alpha 2 (Gnai2) and decrement of Transmembrane protein 100 (Tmem100), Mesenchyme homeobox 2 (Meox2) and Lymphatic vessel hyaluronan Receptor 1 (LYVE1) expression were observed in earlier stage of placentas even before apparent morphological changes occurred, suggesting that these genes are involved in the maintenance of fetal capillaries associated with Peg11/Rtl1 in development.
2016-10-19 | GSE88849 | GEO
Project description:Paternally expressed 11/Retrotransposon-like 1 (Peg11/Rtl1) knockout (KO) mice exhibited mid to late fetal lethality or late fetal growth retardation associated with frequent neonatal lethality. The lethal phenotype was largely dependent on genetic background and became more severe with each succeeding generation in the course of backcross experiments to C57BL/6 (B6). We previously suggested these lethal and growth phenotypes were due to severe defects in placental fetal capillaries in labyrinth layer. In this study, we reexamined KO fetuses exhibiting mid fetal lethality with internal bleeding. Importantly, basal region of fetal capillary network was specially damaged, therefore, also leading to poor expansion of the labyrinth layer and placental size reduction in later stage. Apparent up-regulation of Guanine nucleotide binding protein, alpha 2 (Gnai2) and decrement of Transmembrane protein 100 (Tmem100), Mesenchyme homeobox 2 (Meox2) and Lymphatic vessel hyaluronan Receptor 1 (LYVE1) expression were observed in earlier stage of placentas even before apparent morphological changes occurred, suggesting that these genes are involved in the maintenance of fetal capillaries associated with Peg11/Rtl1 in development.
2016-10-19 | GSE88891 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2016-10-19 | GSE88892 | GEO
Project description:Glucose, the primary energy substrate for fetal oxidative processes and growth, is transferred from maternal to fetal circulation down a concentration gradient by placental facili-tative glucose transporters. In sheep, SLC2A1 and SLC2A3 are the primary transporters available in the placental epithelium, with SLC2A3 located on the maternal-facing apical trophoblast membrane and SLC2A1 located on the fetal-facing basolateral trophoblast membrane. We have previously reported that impaired placental SLC2A3 glucose transport resulted in smaller, hypo-glycemic fetuses with reduced umbilical artery insulin and glucagon concentrations, in addition to diminished pancreas weights. These findings led us to subject RNA derived from SLC2A3-RNAi (RNA interference) and NTS-RNAi (non-targeting sequence) fetal pancreases to qPCR followed by transcriptomic analysis. We identified a total of 771 differentially expressed genes (DEGs). Upregulated pathways were associated with fat digestion and absorption, partic-ularly fatty acid transport, lipid metabolism, and cholesterol biosynthesis, suggesting a potential switch in energetic substrates due to hypoglycemia. Pathways related to molecular transport and cell signaling, including PPAR and PI3K-Akt signaling, as well as negative regulation of cellular proliferation were also impacted. A few genes directly related to gluconeogenesis were also dif-ferentially expressed. Our results suggest that fetal hypoglycemia during the first half of gestation impacts fetal pancreas development and function that is not limited to beta cell function.
2024-04-26 | GSE261932 | GEO
Project description:Intra-uterine growth restriction (IUGR) and fetal overgrowth increase the risk of postnatal health. Maternal nutrition is the major intrauterine environmental factor that alters fetal weight. However, the mechanisms underlying maternal nutrition affect fetal development is not entirely clear. We developed a pig model and used isobaric tags for relative and absolute quantification (iTRAQ) to investigate alterations in the placental proteome were obtained from gilts in normal-energy-intake (Con) and high-energy-intake (HE) group, respectively.At 90 d of gestation, the heavy fetuses were found at the tubal ends and light fetuses at the cervical ends of the uterus in Con group and the heavy fetuses had higher glucose concentration than the light fetuses. However, a higher uniformity was noted in HE group. Placental promote between these two positions indicated that a total of 78 and 50 differentially expressed proteins were detected in Con and HE group, respectively. In Con group, these proteins related to lipid metabolism (HADHA, AACS, CAD), nutrient transport (GLUT, SLC27A1) and energy metabolism (NDUFV1, NDUFV2, ATP5C1). However, the differentially expressed proteins in HE group were mainly participation in transcriptional and translational regulation and intracellular vesicular transport.
2018-10-26 | PXD004951 | Pride
Project description:The placenta acts as an interface between the mother and fetus, regulating nutrient transport and secreting hormones which impact maternal metabolism. Complications during pregnancy, such as placental endocrine malfunction, programme offspring to develop metabolic disease during adulthood, in part via changes in gene expression in critical metabolic organs, such as the liver, during fetal development. Placental endocrine malfunction was induced via the misexpression of two imprinted genes (Igf2 and H19) exclusively in the endocrine zone of the mouse placenta, to study the consequences this has on fetal hepatic gene expression.
2023-11-30 | E-MTAB-11457 | biostudies-arrayexpress
Project description:Purpose: Identify differences in gene expression profiles in fetal monocytes - cells that persist and differentiate postnatally - according to distinct placental histologic domains. Methods: We first isolated classical and intermediate monocyte subsets via FACS and performed transcriptomic profiling of 140 samples (70 classical and 70 intermediate monocyte samples) using bulk RNA-Seq. Results: We report that placental lesions are associated with gene expression changes in fetal monocyte subsets. Specifically,fetal monocytes exposed to acute placental inflammation upregulate biological processes related to monocyte activation, monocyte chemotaxis, and platelet function while monocytes exposed to maternal vascular malperfusion lesions downregulate these processes. Additionally, we show that intermediate monocytes might be a source of mitogens, such as HBEGF, NRG1, and VEGFA, implicated in different outcomes related to prematurity. Conclusions: This is the first study to show that placental lesions are associated with unique changes in fetal monocytes and monocyte subsets. As fetal monocytes persist and differentiate into various phagocytic cells following birth, our study may provide insight into morbidity related to prematurity and ultimately potential therapeutic targets.
2022-02-02 | GSE195727 | GEO
Project description:Myostatin (gene symbol: <i>Mstn</i>) is an autocrine and paracrine inhibitor of muscle growth. Pregnant mice with genetically reduced levels of myostatin give birth to offspring with greater adult muscle mass and bone biomechanical strength. However, maternal myostatin is not detectable in fetal circulations. Fetal growth is dependent on the maternal environment, and the provisioning of nutrients and growth factors by the placenta. Thus, this study examined the effect of reduced maternal myostatin on maternal and fetal serum metabolomes, as well as the placental metabolome. Fetal and maternal serum metabolomes were highly distinct, which is consistent with the role of the placenta in creating a specific fetal nutrient environment. There was no effect from myostatin on maternal glucose tolerance or fasting insulin. In comparisons between pregnant control and <i>Mstn</i><sup>+/-</sup> mice, there were more significantly different metabolite concentrations in fetal serum, at 50, than in the mother's serum at 33, confirming the effect of maternal myostatin reduction on the fetal metabolic milieu. Polyamines, lysophospholipids, fatty acid oxidation, and vitamin C, in fetal serum, were all affected by maternal myostatin reduction.
2023-06-08 | MTBLS3345 | MetaboLights
Project description:This study aims to identify genome-wide placental DNA differential methylation positions (DMPs) in fetal overgrowth and the associations with fetal growth factors, leptin and adiponectin. In the Shanghai Birth Cohort, we studied 30 pairs of placentals of large-for-gestational-age (LGA, birth weight>90th percentile, an indicator of fetal overgrowth) and optimal-for-gestational-age (OGA, 25th-75th percentiles, control) newborns matched by sex and gestational age. Placental DNA methylations were measured by the Illumina Infinium Human Methylation-EPIC BeadChip. Cord blood insulin, C-peptide, proinsulin, IGF-1, IGF-2, leptin and adiponectin concentrations were measured. We identified 543 DMPs (397 hypermethylated, 146 hypomethylated) comparing LGA vs. OGA at false discovery rate <5% and absolute methylation difference >0.05 adjusting for placental cell type heterogeneity, maternal age, pre-pregnancy BMI and HbA1c levels during pregnancy. We validated a hyper-methylated gene - cadherin 13 (CDH13) reported in a previous epigenome-wide association study, and validated a newly discovered differentially (hyper-)methylated gene -visual system homeobox 1 (VSX1) in an independent pyrosequencing study sample (47 LGA-control pairs). Pathway analysis did not detect any statistically significant pathway correcting for multiple tests. Adiponectin in cord blood was correlated with its gene methylation in the placenta, while other observed biomarkers were not. Fetal overgrowth was associated with a large number of altered placental gene DNA methylations. The study provides robust evidence suggesting that placental CDH13 and VSX1 genes are hyper-methylated in LGA. Placental gene methylation was correlated with cord blood biomarker for adiponectin, but not for leptin and fetal growth factors.
2022-12-31 | GSE204977 | GEO
Project description:The labyrinthian fetoplacental capillary network is of vital importance for proper nourishment of the developing embryo. An inadequate function of the maternal-fetal circulation has emerged as one of the primary causes of placental insufficiency. Here, we show that the spatial zonation of the placental labyrinth vasculature is controlled by flow-regulated epigenetic mechanisms. The spatial and temporal analysis of gene transcription revealed a gradual change in the expression of epigenetic enzymes with the de novo DNA methyltransferase 3a (DNMT3A) as primary enzyme introducing DNA methylation in cells of the vascular system. Loss of Dnmt3a resulted in DNA hypomethylation and disturbance of the spatial-zonated placental gene expression. The resulting global DNA hypomethylation impaired the angiogenic capacity of endothelial cells. Global as well as endothelium-predominant deletion of Dnmt3a resulted in impaired placental vascularization and fetal growth retardation. A meta-analysis of human placental endothelial cell gene expression identified an association between preeclampsia and reduction of DNMT3A. Collectively, our study identified DMNT3A as critical methylome-regulator of placental endothelial cell gene expression and function with clinical implications for the pathogenesis of placental dysfunction, as it occurs during preeclampsia or fetal growth retardation.
2024-11-21 | GSE280168 | GEO