Effects of age and sex on gene expression in the mouse heart
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE202384 | GEO | 2022/09/20
REPOSITORIES: GEO
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Project description:Sex differences in behaviors relevant to nicotine addiction have been observed in rodent models and human subjects. Behavioral, imaging and epidemiological studies also suggest underlying sex differences in mesolimbic dopamine signaling pathways. In this study we evaluated the proteome in the ventral tegmental area (VTA) and nucleus accumbens (NAc) shell in male and female mice. Experimental groups included two mouse strains (C3H/HeJ and C57BL/6J) at baseline, a sub-chronic, rewarding regimen of nicotine in C3H/HeJ mice, and chronic nicotine administration and withdrawal in C57BL/6J mice. Isobaric labeling with a TMT 10-plex system, sample fractionation, and tandem mass spectrometry were used to quantify changes in protein abundance. Similar or greater numbers of differentially regulated proteins were found between sexes at baseline in C3H/HeJ or C57BL/6J mice than within sexes following their respective regimen of nicotine administration. Despite differences by sex, strain, and nicotine exposure parameters, glial fibrillary acidic protein (GFAP) and dopamine and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32, Ppp1r1b) were repeatedly identified as significantly altered proteins, especially in the VTA. Further, network analyses showed sex- and nicotine-dependent regulation of a number of signaling pathways, including dopaminergic signaling. Sub-chronic nicotine exposure in female mice increased proteins related to dopaminergic signaling in the NAc shell but decreased them in the VTA, whereas the opposite pattern was observed in male mice. In contrast, dopaminergic signaling pathways were similarly upregulated in both male and female VTA after chronic nicotine and withdrawal. Overall, this study identifies significant sex differences in the proteome of the mesolimbic system, at baseline and after nicotine reward or withdrawal, which may help explain differential trajectories and susceptibility to nicotine addiction in males and females.
2021-06-28 | PXD023859 | Pride
Project description:In this study cDNA microarrays were used to identify genes with sex-biased expression in mouse whole hearts of two age classes (2 months and 8 months of age). Experiment Overall Design: A total of 24 male and female C57BL/6 mice were sacrificed at two and eight months of age, respectively (n=6 per group). Isolated total RNAs were pooled according to sex and age and hybridized on Agilent cDNA microarrays (age-matched, male vs. female or vice versa). Four technical replicates were carried out with exchanged dye-labelled RNA probes (dye-swap) on two of them.
2008-06-13 | E-GEOD-4793 | biostudies-arrayexpress
Project description:Maternal high-fat diet consumption predisposes to metabolic and liver dysfunction in F1 male and female at young adulthood. Purpose: We used RNA-seq to determine the liver transcriptome of male and female F1 of MO and control fed mothers. Methods: Female Wistar rat mothers ate control (C) or obesogenic (MO) diet from the time they were weaned through breeding at postnatal day (PND) 120, delivery and lactation. After weaning all male and female F1 ate control diet. At PND 110 liver and fat were collected to analyze metabolites, histology and liver differentially expressed genes. To identify the functional F1 liver changes due to MO, we evaluated the differentially expressed genes (DEGs) between MO and C males and females with separate pairwise comparisons due to the marked differences between males and females. Genes were filtered based on ≥ 1.4 fold change (FC) and nominal P value <0.05 (Student´s t-test). Results: MOF1 males presented greater physiologic and histological NAFLD characteristics than MOF1 females. RNA-seq revealed 1,365 genes significantly changed in male MOF1 liver and only 70 genes in MOF1 female compared with controls. GO and KEGG analysis identified differentially expressed genes related to metabolic process. Male MOF1 liver showed the following altered pathways: insulin signaling (22 genes), phospholipase D signaling (14 genes), NAFLD (13 genes), and glycolysis/ gluconeogenesis (7 genes). In contrast, few genes were altered in these pathways in MOF1 females. Conclusions: These results improve understanding of the mechanism by which a maternal high fat diet affects their F1. In summary, MO programs sex-dependent F1 changes in insulin, glucose and lipid signaling pathways, leading to liver dysfunction and insulin resistance. Male adult MOF1 livers show global down-regulation of genes that are required for normal function of major liver metabolic pathways. This new knowledge is important for producing sex-specific interventions.
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Project description:Heart failure represents a leading cause of mortality in the elderly population. Although aging features include diastolic dysfunction and interstitial fibrosis in both males and females, it becomes increasingly apparent that aged male and female hearts are phenotypically different. There were fundamental differences in extracellular matrix (ECM) composition and architecture and heart function indices at the baseline, which were further accentuated by Aicar treatment. By combining in vivo, ex vivo, and in vitro strategies, we demonstrated that there are sex-specific features that influence the response to pharmacological intervention in the aging mouse heart.
2022-06-23 | PXD031223 | Pride
Project description:In this study cDNA microarrays were used to identify genes with sex-biased expression in mouse whole hearts of two age classes (2 months and 8 months of age). Keywords: cDNA microarray hybridization, sex-specific expression
2006-07-09 | GSE4793 | GEO
Project description:We isolated mRNA from adult mouse (C57BL/6J background) hearts and performed mRNA micro-array analysis to compare gene expression profiles between control and Rhau-deletion mice (inducible deletion by tamoxifen).
2021-03-18 | GSE119384 | GEO
Project description:C57Bl/6J mice received continuous administration of saline or Angiotensin II via implanted minipumps for 7 days, total RNA prepared from homogenized hearts, SAGE library constructed from heart RNA pooled from 6 mice. Keywords: other
2004-07-22 | GSE1446 | GEO
Project description:Aging impairs the mitochondrial electron transport chain (ETC), especially in interfibrillar mitochondria (IFM). Mitochondria are in close contact with the endoplasmic reticulum (ER). Induction of ER stress leads to ETC injury in adult heart mitochondria. We asked if ER stress contributes to the mitochondrial dysfunction during aging. Subsarcolemmal mitochondria (SSM) and IFM were isolated from 3, 18, and 24 mo. C57Bl/6 mouse hearts. ER stress progressively increased with age, especially in 24 mo. mice that manifest mitochondrial dysfunction. OXPHOS was decreased in 24 mo. IFM oxidizing complex I and complex IV substrates. Proteomic analysis showed that the content of multiple complex I subunits was decreased in IFM from 24 mo. hearts, but remained unchanged in in 18 mo. IFM without a decrease in OXPHOS. Feeding mice with 4-phenylbutyrate (4-PBA) for two weeks attenuated the ER stress and improved mitochondrial function in 24 mo. mice. These results indicate that ER stress contributes to the mitochondrial dysfunction in aged hearts. Attenuation of ER stress is a potential approach to improve mitochondrial function in aged hearts.
2020-07-23 | PXD018545 | Pride
Project description:Heart failure and other cardiomyopathies have distinct presentations in males versus females that are often overlooked, leading to ineffective treatment, and contributing to the growing mortality from heart diseases. Understanding the differences in the pathogenesis of heart disease in males and females can guide early diagnostics and sex-specific therapy. Thus, there is a pressing need to investigate the sex-specificity of promoter and enhancer activity in the pathogenesis of heart failure. Here, using cap analysis of gene expression we characterize the sex-specific activity of transcriptional regulatory elements in 17 male and 14 female healthy and failing hearts. We show that differentially expressed transcribed regulatory elements between two sexes are spread throughout the entire genome in healthy and failing atria and ventricles, and are related to immune system, metabolic, cardiomyocyte function, and developmental pathways. Moreover, we found 720 genes with sex-dependent promoter switching of which 40 switched dominant promoters. Among those was CREM, a transcription factor, with a short repressive dominant isoform exclusive for males. CREM is related to extensive β-adrenergic receptor stimulation that leads to elevated arrhythmic activity, hypertrophy and heart dysfunction. Furthermore, we identified metabolic pathways being more responsible for female aging and developmental pathways for male aging. We also showed sex-specific aging patterns, such as age-specific promoter usage of 1,100 genes that behaved differently depending on sex, including UCKL1 and HAND2 linked to uridine metabolism and cardiac development, respectively.
2023-04-27 | GSE212695 | GEO
Project description:C57Bl/6J mice received continuous administration of saline or Angiotensin II via implanted minipumps for 7 days, total RNA prepared from homogenized hearts, SAGE library constructed from heart RNA pooled from 6 mice. Keywords: other
2004-07-22 | E-GEOD-1446 | biostudies-arrayexpress