Sex-Specific Differences in MicroRNA Expression during Human Fetal Lung Development
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE200153 | GEO | 2022/05/05
REPOSITORIES: GEO
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Project description:Sex differences in the incidence and prognosis of respiratory diseases have been reported. Studies have shown that women are at increased risk of adverse health outcomes from air pollution than men, but sex-specific immune gene expression patterns and regulatory networks have not been well studied in the lung. MicroRNAs (miRNAs) are environmentally sensitive posttranscriptional regulators of gene expression that may mediate the damaging effects of inhaled pollutants in the lung, by altering the expression of innate immunity molecules. Here, male and female mice of the C57/Bl6 background were exposed to 2ppm of ozone or filtered air (control) for 3 hours. Female mice were also exposed at different stages of the estrous cycle. Following exposure, lungs were harvested and total RNA was extracted. We used PCR arrays to study sex-differences in the expression of 84 miRNAs predicted to target inflammatory and immune genes. Our results identified differentially expressed miRNA signatures in the lungs of male vs. female exposed to ozone. In silico pathway analyses identified sex-specific biological networks affected by exposure to ozone that ranged from direct predicted gene targeting to complex interactions with multiple intermediates. We also identified differences in miRNA expression and predicted regulatory networks in females exposed to ozone at different estrous cycle stages. These results indicate that both sex and hormonal status can influence lung miRNA expression in response to ozone exposure, indicating that sex-specific miRNA regulation of inflammatory gene expression could mediate differential pollution-induced health outcomes in men and women.
2018-03-13 | GSE111667 | GEO
Project description:MicroRNA expression levels were assessed during the pseudoglandular phase of normal fetal lung development at the critical time, when the the conducting airways are formed. Precise miRNA regulation is important for proper pulmonary organogenesis, supporting the delicate balance between expansion of progenitor cells and their terminal differentiation. Microarray analyses could indicate the potential involvement of miRNAs important for human pulmonary hypoplasia. Two replicates of pooled RNA from two 9 week old fetal lung samples
2016-02-05 | E-GEOD-76919 | biostudies-arrayexpress
Project description:MicroRNA expression levels were assessed during the pseudoglandular phase of normal fetal lung development at the critical time, when the the conducting airways are formed. Precise miRNA regulation is important for proper pulmonary organogenesis, supporting the delicate balance between expansion of progenitor cells and their terminal differentiation. Microarray analyses could indicate the potential involvement of miRNAs important for human pulmonary hypoplasia.
2016-02-05 | GSE76919 | GEO
Project description:Global miRNA expression was examined in liver tissues from male and female F344 rats over the life span for the purpose of evaluating their possible roles in susceptibility to liver toxicity and disease. Hepatic miRNA expression was characterized at 2, 5, 6, 8, 15, 21, 52, 78, and 104 weeks of age in both sexes using Agilent 8x15k rat miRNA microarrays containing multiple probes for 677 unique miRNAs. Data processing, 75% normalization, and statistical analysis of microarray data were performed in SAS. Functional analysis (Ingenuity) was performed on select miRNAs exhibiting prominent age and sex expression differences. +
2017-02-19 | GSE65169 | GEO
Project description:MicroRNAs (miRNAs) are regulatory noncoding RNAs that affect the production of a significant fraction of human mRNAs via post-transcriptional regulation. Interindividual variation of the miRNA expression levels is likely to influence the expression of miRNA target genes and may therefore contribute to phenotypic differences in humans, including susceptibility to common disorders. The extent to which miRNA levels are genetically controlled is largely unknown. In this report, we assayed the expression levels of miRNAs in primary fibroblasts from 180 European newborns of the GenCord project and performed association analysis to identify eQTLs (expression quantitative traits loci). We detected robust expression for 121 miRNAs out of 365 interrogated. We have identified significant cis- (10%) and trans- (11%) eQTLs. Furthermore, we detected one genomic locus (rs1522653) that influences the expression levels of five miRNAs, thus unraveling a novel mechanism for coregulation of miRNA expression
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Project description:Kidney miRNA expression was examined in F344 rats at 2, 5, 6, 8, 15, 21, 78, and 104 weeks of age in both sexes using Agilent miRNA microarrays. 311 miRNAs were found to be expressed in at least one age and sex. Filtering criteria of ≥1.5 fold change and ANOVA (FDR <5%) revealed 174 differentially expressed miRNAs in the kidney; 173 and 34 miRNAs exhibiting age and sex effects, respectively. Principal component analysis revealed age effects predominated over sex effects, with 2 week miRNA expression being much different from other ages. No significant sexually dimorphic miRNA expression was observed from 5 to 8 weeks, while the most differential expression (13 miRNAs) was observed at 21 weeks. Potential target genes of these differentially expressed miRNAs were identified. Pathway analysis was used to investigate the possible roles of these target genes in age- and sex-specific differences.
2015-01-10 | GSE64842 | GEO
Project description:Paladin (Pald1, mKIAA1274 or x99384) was identified in screens for vascular-specific genes and is a putative phosphatase. We have demonstrated that paladin has a predominant vascular expression pattern and shifts from endothelial to mural cells during mouse development. We have now characterized the Pald1 knock-out mouse in a broad array of behavioral, physiological and biochemical tests. Here, we show that female, but not male, Pald1 heterozygous and homozygous knock-out mice displayed an emphysema-like phenotype with increased alveolar air spaces and impaired lung function with obstructive changes. In contrast to many other tissues where Pald1 is restricted to the vascular compartment, Pald1 is expressed in both the epithelial and mesenchymal compartments of the postnatal lung. However, in Pald1 knock-out females, there is a specific increase in apoptosis and proliferation of endothelial cells, but not in non-endothelial cells. This results in a transient reduction of endothelial cells in the maturing lung. Our data suggests that paladin is required during lung vascular development and for normal function of the developing and adult lung in a sex-specific manner. To our knowledge, this is the first report of a sex-specific effect on endothelial cell apoptosis.
Proteomic analysis of Pald1 wild type and knock-out mice reveal that most of the protein expression differences are related to sex and not genotype, supporting the notion that sex can be a major factor for lung development and disease. In addition, Pald1 wild type and knock-out mice exhibit differential expression of HPGD, hydroxyprostaglandin dehydrogenase 15 (NAD), the major enzyme for degradation of prostaglandins.
2017-11-01 | PXD005625 | JPOST Repository
Project description:MicroRNAs (miRNAs) are a highly conserved class of small RNAs which function in a sequence-specific manner to post-transcriptionally regulate expression of target genes. Tissue-specific miRNA expression studies have discovered numerous functions for miRNAs in various aspects of embryonic development, but a role for miRNAs in gonadal development and sex differentiation has not yet been reported. Using the chicken embryo as a vertebrate model, differential miRNA expression between male and female embryonic gonads, was analysed at three developmental stages (embryonic days (E) 5.5, E6.5 and E9.5), using custom-designed 4x2K CombiMatrix miRNA microarray. The aims of this study were to: 1-identify miRNAs differentialy expressed by sex; 2-identify sex-specific miRNAs; 3-analyse global changes in miRNA up-regulation in male versus female gonads before, during and after the histological onset of sexual differentiation. This study provides a basis for establishing whetehr miRNAs are involved in either initiating or regulating vertebrate gonadal sex differentiation. Keywords: miRNA, sex comparison, developmental stage comparison.
2008-10-11 | GSE13154 | GEO
Project description:Sex is a key modifier of neurological disease outcomes. Microglia are implicated in neurological diseases and modulated by miRNAs, but it is unknown whether microglial miRNAs have sex-specific influences on disease. We show that microglial miRNA expression differs in males and females, and loss of miRNAs leads to sex-specific changes in the microglial transcriptome and to tau pathology. These findings suggest microglial miRNAs influence tau pathogenesis in a sex-specific manner.
2019-11-05 | GSE122663 | GEO
Project description:Sex is a key modifier of neurological disease outcomes. Microglia are implicated in neurological diseases and modulated by miRNAs, but it is unknown whether microglial miRNAs have sex-specific influences on disease. We show that microglial miRNA expression differs in males and females, and loss of miRNAs leads to sex-specific changes in the microglial transcriptome and to tau pathology. These findings suggest microglial miRNAs influence tau pathogenesis in a sex-specific manner.
2019-11-05 | GSE135330 | GEO