Transcription profiling of human genital fibroblasts of normal males and 46,XY females with androgen insensitivity syndrome
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Janos Demeter
PROVIDER: E-SMDB-2121 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Publications
Differential gene-expression patterns in genital fibroblasts of normal males and 46,XY females with androgen insensitivity syndrome: evidence for early programming involving the androgen receptor.
Holterhus Paul-Martin PM Hiort Olaf O Demeter Janos J Brown Patrick O PO Brooks James D JD
Genome biology 20030515 6
<h4>Background</h4>Androgen insensitivity syndrome (AIS) comprises a range of phenotypes from male infertility to complete feminization. Most individuals with AIS carry germline mutations of the androgen receptor (AR) that interfere with or ablate its function. As genital fibroblasts retain expression of the AR in vitro, we used genital skin fibroblasts from normal males and 46,XY females with complete AIS due to known AR mutations to gain insights into the role of the AR in human genital differ ...[more]
Similar Datasets
Project description:Abstract: BACKGROUND: Androgen insensitivity syndrome (AIS) comprises a range of phenotypes from male infertility to complete feminization. Most individuals with AIS carry germline mutations of the androgen receptor (AR) that interfere with or ablate its function. As genital fibroblasts retain expression of the AR in vitro, we used genital skin fibroblasts from normal males and 46,XY females with complete AIS due to known AR mutations to gain insights into the role of the AR in human genital differentiation. RESULTS: Using DNA microarrays representing 32,968 different genes, we identified 404 transcripts with significant differences in transcription levels between genital skin fibroblasts cultured from normal and AIS-affected individuals. Gene-cluster analyses uncovered coordinated expression of genes involved in key processes of morphogenesis. On the basis of animal studies and human genetic syndromes, several of these genes are known to have specific roles in genital differentiation. Remarkably, genital fibroblasts from both normal and AIS-affected individuals showed no transcriptional response to dihydrotestosterone treatment despite expression of the AR. CONCLUSIONS: The results suggest that in addition to differences in the anatomic origin of the cells, androgen signaling during prenatal development contributes to setting long-lasting, androgen-independent transcriptional programs in genital fibroblasts. Our findings have broad implications in understanding the establishment and the stability of sexual dimorphism in human genital development. This SuperSeries is composed of the SubSeries listed below.
2006-03-07 | GSE4353 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE3871: Effects of androgen treatment on genital fibroblasts GSE3872: Baseline gene transcription in genital fibroblasts Abstract: BACKGROUND: Androgen insensitivity syndrome (AIS) comprises a range of phenotypes from male infertility to complete feminization. Most individuals with AIS carry germline mutations of the androgen receptor (AR) that interfere with or ablate its function. As genital fibroblasts retain expression of the AR in vitro, we used genital skin fibroblasts from normal males and 46,XY females with complete AIS due to known AR mutations to gain insights into the role of the AR in human genital differentiation. RESULTS: Using DNA microarrays representing 32,968 different genes, we identified 404 transcripts with significant differences in transcription levels between genital skin fibroblasts cultured from normal and AIS-affected individuals. Gene-cluster analyses uncovered coordinated expression of genes involved in key processes of morphogenesis. On the basis of animal studies and human genetic syndromes, several of these genes are known to have specific roles in genital differentiation. Remarkably, genital fibroblasts from both normal and AIS-affected individuals showed no transcriptional response to dihydrotestosterone treatment despite expression of the AR. CONCLUSIONS: The results suggest that in addition to differences in the anatomic origin of the cells, androgen signaling during prenatal development contributes to setting long-lasting, androgen-independent transcriptional programs in genital fibroblasts. Our findings have broad implications in understanding the establishment and the stability of sexual dimorphism in human genital development. Refer to individual Series
2006-03-06 | E-GEOD-4353 | biostudies-arrayexpress
Project description: Not available
2005-10-13 | E-SMDB-2119 | biostudies-arrayexpress
Project description:BackgroundAndrogen insensitivity syndrome (AIS) comprises a range of phenotypes from male infertility to complete feminization. Most individuals with AIS carry germline mutations of the androgen receptor (AR) that interfere with or ablate its function. As genital fibroblasts retain expression of the AR in vitro, we used genital skin fibroblasts from normal males and 46,XY females with complete AIS due to known AR mutations to gain insights into the role of the AR in human genital differentiation.ResultsUsing DNA microarrays representing 32,968 different genes, we identified 404 transcripts with significant differences in transcription levels between genital skin fibroblasts cultured from normal and AIS-affected individuals. Gene-cluster analyses uncovered coordinated expression of genes involved in key processes of morphogenesis. On the basis of animal studies and human genetic syndromes, several of these genes are known to have specific roles in genital differentiation. Remarkably, genital fibroblasts from both normal and AIS-affected individuals showed no transcriptional response to dihydrotestosterone treatment despite expression of the AR.ConclusionsThe results suggest that in addition to differences in the anatomic origin of the cells, androgen signaling during prenatal development contributes to setting long-lasting, androgen-independent transcriptional programs in genital fibroblasts. Our findings have broad implications in understanding the establishment and the stability of sexual dimorphism in human genital development.
| S-EPMC193616 | biostudies-literature
Project description:This gene set contains skin fibroblasts from either labia majora of 46,XY sex reversed females having complete androgen insensitivity syndrome due to inactivation mutations of the androgen receptor gene and from the scrotum of normal males. Both, labia majora and scrotum origin from the same embryological anlagen, the labioscrotal swellings. The phenotypic difference is due to androgen dependent virilization in males. This is not possible in 46,XY patients with complete androgen insensitivity syndrome because the androgen receptor pathway is knocked out. A cell type comparison design experiment design type compares cells of different type for example different cell lines. Cell Line: genital skin fibroblasts from different locations mutant line: normal 46,XY male and 46,XY sex reversed female due to inactivating mutations of the androgen receptor gene Computed
2010-06-25 | E-GEOD-6797 | biostudies-arrayexpress
Project description:This gene set contains skin fibroblasts from either labia majora of 46,XY sex reversed females having complete androgen insensitivity syndrome due to inactivation mutations of the androgen receptor gene and from the scrotum of normal males. Both, labia majora and scrotum origin from the same embryological anlagen, the labioscrotal swellings. The phenotypic difference is due to androgen dependent virilization in males. This is not possible in 46,XY patients with complete androgen insensitivity syndrome because the androgen receptor pathway is knocked out. A cell type comparison design experiment design type compares cells of different type for example different cell lines. Cell Line: genital skin fibroblasts from different locations mutant line: normal 46,XY male and 46,XY sex reversed female due to inactivating mutations of the androgen receptor gene Keywords: cell_type_comparison_design
2007-10-20 | GSE6797 | GEO
Project description:BackgroundTo better understand the molecular programs of normal and abnormal genital development, clear-cut definition of androgen-dependent gene expression patterns, without the influence of genotype (46, XX vs. 46, XY), is warranted. Previously, we have identified global gene expression profiles in genital-derived fibroblasts that differ between 46, XY males and 46, XY females with complete androgen insensitivity syndrome (CAIS) due to inactivating mutations of the androgen receptor (AR). While these differences could be due to cell autonomous changes in gene expression induced by androgen programming, recent work suggests they could also be influenced by the location from which the fibroblasts were harvested (topology). To minimize the influence of topology, we compared gene expression patterns of fibroblasts derived from identical urogenital anlagen: the scrotum in normally virilized 46, XY males and the labia majora from completely feminized 46, XY individuals with CAIS.Results612 transcripts representing 440 unique genes differed significantly in expression levels between scrotum and CAIS labia majora, suggesting the effects of androgen programming. While some genes coincided with those we had identified previously (TBX3, IGFBP5, EGFR, CSPG2), a significant number did not, implying that topology had influenced gene expression in our previous experiments. Supervised clustering of gene expression data derived from a large set of fibroblast cultures from individuals with partial AIS revealed that the new, topology controlled data set better classified the specimens.ConclusionInactivating mutations of the AR, in themselves, appear to induce lasting changes in gene expression in cultured fibroblasts, independent of topology and genotype. Genes identified are likely to be relevant candidates to decipher androgen-dependent normal and abnormal genital development.
| S-EPMC2212662 | biostudies-literature
Project description:This dataset contains fibroblasts from different genital and extragenital regions, mostly from 46,XY individuals. Due to proven androgen receptor gene mutations, several individuals have varying degrees of undervirilization of the external genitalia ranging from complete androgen insensitivity syndrome (CAIS) to partial androgen insensitivity syndrome (PAIS). CAIS is a completely female person despite a 46,XY karyotype. AIS-3 individuals have ambigous external genitalia. AIS-4 means predominantly female (clitoral enlargement), AIS-2 means predominantly male (hypospadias). It is important for this experiment set, that it contains data from 3 differet independent datasets that are not directly cmparable with each other. This is because of different reference RNAs and different glass slides. The particular normalization procedure is described in the paper accompanying this dataset. Only then, all arrays are allowed to be clustered together. Dataset 2 and 3 have "DS-2" and "DS-3" in their experiment names. All other experiments belong to dataset 1. A cell type comparison design experiment design type compares cells of different type for example different cell lines. Disease State: normal male, normal female or ambiguous external genitalia according to grading scheme by Sinnecker et al. Cell Line: fibroblast cell lines from different regions of the genital skin, some from extragenital skin Sex/Mating type: 46,XY or 46,XX karyotype Computed
2010-06-25 | E-GEOD-6796 | biostudies-arrayexpress
Project description:This dataset contains fibroblasts from different genital and extragenital regions, mostly from 46,XY individuals. Due to proven androgen receptor gene mutations, several individuals have varying degrees of undervirilization of the external genitalia ranging from complete androgen insensitivity syndrome (CAIS) to partial androgen insensitivity syndrome (PAIS). CAIS is a completely female person despite a 46,XY karyotype. AIS-3 individuals have ambigous external genitalia. AIS-4 means predominantly female (clitoral enlargement), AIS-2 means predominantly male (hypospadias). It is important for this experiment set, that it contains data from 3 differet independent datasets that are not directly cmparable with each other. This is because of different reference RNAs and different glass slides. The particular normalization procedure is described in the paper accompanying this dataset. Only then, all arrays are allowed to be clustered together. Dataset 2 and 3 have "DS-2" and "DS-3" in their experiment names. All other experiments belong to dataset 1. A cell type comparison design experiment design type compares cells of different type for example different cell lines. Disease State: normal male, normal female or ambiguous external genitalia according to grading scheme by Sinnecker et al. Cell Line: fibroblast cell lines from different regions of the genital skin, some from extragenital skin Sex/Mating type: 46,XY or 46,XX karyotype Keywords: cell_type_comparison_design
2007-10-20 | GSE6796 | GEO
Project description:The aim of this study was to search for clinical and laboratorial data in 46,XY patients with ambiguous genitalia (AG) and normal testosterone (T) synthesis that could help to distinguish partial androgen insensitivity syndrome (PAIS) from 5?-reductase type 2 deficiency (5?-RD2) and from cases without molecular defects in the AR and SRD5A2 genes. Fifty-eight patients (51 families) were included. Age at first evaluation, weight and height at birth, consanguinity, familial recurrence, severity of AG, penile length, LH, FSH, T, dihydrotestosterone (DHT), ?4-androstenedione (?4), and T/DHT and T/?4 ratios were evaluated. The AR and SRD5A2 genes were sequenced in all cases. There were 9 cases (7 families) of 5?-RD2, 10 cases (5 families) of PAIS, and 39 patients had normal molecular analysis of SRD5A2 and AR genes. Age at first evaluation, birth weight and height, and T/DHT ratio were lower in the undetermined group, while penile length was higher in this group. Consanguinity was more frequent and severity of AG was higher in 5?-RD2 patients. Familial recurrence was more frequent in PAIS patients. Birth weight and height, consanguinity, familial recurrence, severity of AG, penile length, and T/DHT ratio may help the investigation of 46,XY patients with AG and normal T synthesis.
| S-EPMC3238364 | biostudies-literature