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Maternal obesity affects fetal neurodevelopmental and metabolic gene expression

ABSTRACT: To investigate fetal gene expression in obese compared to lean women in the second trimester, by performing global gene expression analysis of amniotic fluid (AF) cell-free RNA Analysis of paired data from obese cases and lean controls revealed differential expression of 205 genes. Functional analysis of differentially expressed genes suggested down-regulation of apoptosis in fetuses of obese women, particularly within nervous system pathways involving the cerebral cortex, and activation of pro-estrogenic, pro-inflammatory transcriptional regulators. Prospective whole transcriptome microarray study analyzing cell-free RNA in AF from obese cases and lean controls in the second trimester. Significantly differentially-regulated genes in fetuses of obese cases (N= 8) vs. matched lean controls (N = 8) were identified and functional analyses were performed. Tissue-specific differential gene expression in fetuses of obese women was also examined.

ORGANISM(S): Homo sapiens

SUBMITTER: Heather Wick

PROVIDER: E-GEOD-48521 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Maternal obesity affects fetal neurodevelopmental and metabolic gene expression

Project description:To investigate fetal gene expression in obese compared to lean women in the second trimester, by performing global gene expression analysis of amniotic fluid (AF) cell-free RNA Analysis of paired data from obese cases and lean controls revealed differential expression of 205 genes. Functional analysis of differentially expressed genes suggested down-regulation of apoptosis in fetuses of obese women, particularly within nervous system pathways involving the cerebral cortex, and activation of pro-estrogenic, pro-inflammatory transcriptional regulators.

2013-07-04 | GSE48521 | GEO

The amniotic fluid transcriptome: a source of novel information about human fetal development

Project description:Amniotic fluid (AF) is a complex biological material that provides a unique window into the developing human. Residual AF supernatant contains cell-free fetal RNA. The objective of this study was to develop an understanding of the AF core transcriptome by identifying the transcripts ubiquitously present in the AF supernatant of euploid midtrimester fetuses. We detected 476 well-annotated genes present in all twelve AF samples. Functional analysis identified 6 physiological systems represented in the AF core transcriptome, including musculoskeletal and nervous system development and function and embryonic/ organismal development. mTOR signaling was identified as a key canonical pathway. Twenty-three highly organ-specific transcripts were identified; six of these are known to be highly expressed by fetal brain. This study demonstrates that AF cell-free fetal RNA can provide biological information about multiple fetal organ systems. This was an in silico investigation of gene expression in 12 euploid midtrimester AF samples acquired primarily for advanced maternal age. We focused on the transcripts called M-bM-^@M-^\presentM-bM-^@M-^] in all of the samples. Functional analyses were performed using Ingenuity software. Fetal-organ specificity was examined for each transcript using the GNF Gene Expression Atlas. For fetal organs not represented in the atlas, manual literature searching and Ingenuity analysis were used.

2012-01-11 | E-GEOD-33168 | biostudies-arrayexpress

Expression profiles of amniotic fluid from human fetuses with Down syndrome and euploid controls

Project description:In order to characterize the differences between second trimester Down syndrome (DS) and euploid fetuses, we compared gene expression in uncultured amniotic fluid supernatant samples. We identified individually differentially expressed genes via paired t-tests in the matched samples, and a set of differentially expressed genes on chromosome 21 using Gene Set Enrichment Analysis. Functional pathway analysis of the resulting genes highlighted the importance of oxidative stress, ion transport, and G-protein signaling in the DS fetuses. We profiled seven DS expression samples and seven controls matched for gender and approximate gestational age..

2009-05-21 | E-GEOD-16176 | biostudies-arrayexpress

Global gene expression analysis of amniotic fluid cell-free RNA from recipient twins with twin-twin transfusion syndrome [Set 2]

Project description:To understand the biological pathways involved in twin-twin transfusion syndrome (TTTS) by performing global gene expression analysis of amniotic fluid (AF) cell-free RNA Analysis of paired data from TTTS cases and controls revealed differential expression of 801 genes, which were significantly enriched for neurological disease and cardiovascular system pathways. We also identified cardiovascular genes and pathways associated with the presence of critically abnormal Doppler measurements in Stage III TTTS recipients. Prospective whole transcriptome microarray study analyzing cell-free RNA in AF from TTTS recipient twins and singleton controls. Significantly differentially-regulated genes in TTTS cases (N= 8) vs. matched controls (N = 8) were identified and pathways analyses performed. Significant gene expression differences between Stage II TTTS recipients (N = 5) and Stage III TTTS recipients with abnormal Doppler measurements (N = 5) were also analysed.

2013-05-28 | E-GEOD-47393 | biostudies-arrayexpress

Global gene expression analysis of amniotic fluid cell-free RNA from recipient twins with twin-twin transfusion syndrome [Set 1]

2013-05-28 | E-GEOD-47392 | biostudies-arrayexpress

Expression profiles of amniotic fluid from human fetuses with Trisomy 18 and euploid controls

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2010-12-03 | E-GEOD-25634 | biostudies-arrayexpress

Global Gene Expression Analysis of Term Amniotic Fluid Cell-Free Fetal RNA

Project description:The objective of this study was to identify the tissue expression patterns and biological pathways enriched in term amniotic fluid cell-free fetal RNA by comparing functional genomic analyses of term and second-trimester amniotic fluid supernatants. There were 2,871 significantly differentially regulated genes. In term amniotic fluid, tissue expression analysis showed enrichment of salivary gland, tracheal, and renal transcripts as compared with brain and embryonic neural cells in the second trimester. Functional analysis of genes upregulated at term revealed pathways that were highly specific for postnatal adaptation such as immune function, digestion, respiration, carbohydrate metabolism, and adipogenesis. Inflammation and prostaglandin synthesis, two key processes involved in normal labor, were also activated in term amniotic fluid. This was a prospective whole genome microarray study comparing eight amniotic fluid samples collected from eight women at term who underwent prelabor cesarean delivery and eight second-trimester amniotic fluid samples from routine amniocenteses. A functional annotation tool was used to compare tissue expression patterns in term and second-trimester samples. Pathways analysis software identified physiologic systems, molecular and cellular functions, and upstream regulators that were significantly overrepresented in term amniotic fluid.

2013-04-23 | E-GEOD-46286 | biostudies-arrayexpress

Amniotic fluid RNA gene expression profiling provides insights into the phenotype of Turner syndrome

Project description:Background: Turner syndrome, a common sex chromosome aneuploidy, has characteristics and malformations associated with the phenotype. Fetal amniotic fluid is a complex biological material that could contribute to the understanding Turner syndrome pathogenesis. Global gene expression analysis of Turner syndrome fetal amniotic fluid supernatant was utilized to identify organ systems and specific genes that may play a role in the pathophysiologic changes that are seen in individuals with Turner syndrome. Methods: Global gene expression analysis was performed utilizing cell-free RNA from five midtrimester fetuses with Turner syndrome matched with five euploid female fetuses. Total RNA was extracted, amplified, hybridized onto GeneChipM-BM-. Human Genome U133 Plus 2.0 arrays. Network and pathway analysis of differentially expressed genes were completed. Chromosomal distribution of gene expression differences, differential expression by pathway and organ system (a M-bM-^@M-^\Turner syndrome core transcriptomeM-bM-^@M-^]), and candidate genes that could play a pathological role were identified. Results: There were 470 differentially expressed genes identified in the Turner syndrome transcriptome. The differentially expressed genes were distributed randomly across different chromosomes. Among genes on the X chromosome, XIST was down-regulated, and SHOX not differentially expressed. The most highly represented organ systems were hematologic/immune and neurologic. Increased representation of differentially expressed genes in the hematologic/immune system distinguishes the Turner syndrome transcriptome from the euploid, trisomy 18 and trisomy 21 transcriptomes previously studied in our laboratory. Manual curation of the differentially expressed gene list identified genes including NFATC3, IGFBP5, and LDLR that warrant further study. 2nd trimester amniotic fluid mRNA expression was compared between 5 Turners and 5 euploid fetuses.

2014-06-13 | E-GEOD-58435 | biostudies-arrayexpress

Lipid metabolism genes in first trimester placenta

Project description:Placentas of obese women have low mitochondrial beta-oxidation of fatty acids (FA) and accumulate lipids in late pregnancy. This creates a lipotoxic environment, impairing placental efficiency. We assessed expression of key regulators of FA metabolism in first trimester placentas of lean and obese women. Expression of genes associated with FA oxidation (FAO; ACOX1, CPT2, AMPKα), FA uptake (LPL, LIPG, MFSD2A), FA synthesis (ACACA) and storage (PLIN2) were significantly reduced in placentas of obese compared to lean women. This effect was exacerbated in placentas of male fetuses. The PPARα pathway was enriched for placental genes impacted by obesity. These results demonstrate that obesity and hyperlipidemia impact placental FA metabolism as early as 7 weeks of pregnancy.

2022-10-12 | GSE206037 | GEO

RNA-Seq and expression microarray highlight different aspects of the fetal amniotic fluid transcriptome [microarray]

Project description:The second trimester fetal transcriptome can be assessed based on cell-free RNA found within the amniotic fluid supernatant. The objective of this study was to compare the suitability of two technologies for profiling the human fetal transcriptome: RNA-Seq and expression microarray. Comparisons were based on total numbers of gene detected, rank-order gene expression, and functional genomic analysis. Fewer gene transcripts were observed using RNA-Seq than microarray (4,158 vs 8,842). Correlation of total expression within each sample ranged from R=0.43 to R=0.57. On average, there was 59% concordance in gene identity among the top 10% of genes ranked by expression. The RNA-Seq data yielded more significant pathways enrichment within the ?Physiological Systems Development and Function? categories of IPA. Alternative splicing of many well-known genes, including those previously studied in fetal development, such as H19 and IGF2 is detected by RNA-Seq. Also included in this paper is discussion of the technical challenges inherent to working with cell-free fetal RNA and possible solutions. Cell-free fetal RNA from the amniotic fluid supernatant of five second trimester fetuses was divided and prepared in tandem for analysis using either the Illumina HiSeq 2000 or Affymetrix HG-U133 Plus 2.0 GeneChip microarray.

2014-05-27 | E-GEOD-49891 | biostudies-arrayexpress

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