Testicular gene expression profiles in infertile patients with AZFc deletions of the Y chromosome
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE14310 | GEO | 2010/10/04
SECONDARY ACCESSION(S): PRJNA111309
REPOSITORIES: GEO
Similar Datasets
Project description:In the present study we carried out testicular gene expression profiling of patients with AZFc microdeletion, idiopathic infertility and normal spermatogenesis, in order to identify up- and downregulated genes in the different conditions, and to verify the presence of specific molecular pathways leading to the spermatogenic damage in patients with AZFc deletions. All samples of patients with AZFc deletion clustered together, showing downregulation of several genes related to spermatogenesis. In this study, we analyzed testis expression profiles of 16 patients with different phenotypes, including men with AZFc deletions and men with idiopathic infertility. All pathological human testis RNAs were hybridized against normal testis reference RNA samples (obstructive azoospermia), while the three samples with normal spermatogenesis were hybridized against a control represented by an home-made RNA universal reference consisting of a commercial human purified tissue RNA pool (brain, liver, muscle and lung) (Clontech, Terra Bella, CA, USA) . These latter hybridizations were carried out in order to generate a profile of genes specifically expressed in normal testis.
2010-10-04 | E-GEOD-14310 | biostudies-arrayexpress
Project description:Objective: Klinefelter Syndrome (KS) is the most common sexual chromosome abnormality (47,XXY) and represents the first genetic cause of male infertility. The mechanisms leading to KS testis degeneration are still unclear and no therapy is so far available for affected patients. The present study is aimed to unravel information about molecules playing a key role in the disruption of the spermatogenesis. Design: Gene expression profiles analysis of KS azoospermic testis versus normal testis, could provide useful information about the molecular basis of the alteration of the spermatogenesis. Materials and Methods: Transcriptome analysis was performed carrying out gene expression profile by a whole genome microarray approach on testis biopsies obtained from 6 azoospermic non-mosaic KS men and from 3 controls, for a total of 12 experiments. T-test and False Discovery Rate were used to evaluate differentially expressed genes. Identified transcripts were analysed by Ingenuity Pathways Analysis software to disclose genes biological functions. Results: Data analysis revealed the differentially up- and down-expression, in KS testis versus the control ones, of 656 and 247 genes related to Endocrine system development and function, Lipid metabolism, Reproductive disease, Free radical scavenging, and Cell death. Conclusions: Take together these data show the presence of several genes involved in testis microenvironment deregulation leading to the spermatogenesis failure. This information, associated with an early diagnosis could help to unravel possible therapeutic targets for testis failure prevention and limitation. Gene expression profile of 6 azoospermic KS testicular biopsies versus 3 pooled control testicular biposies form patients with normal spermatogenesis. A total of 12 experiments was carried out including biological and technical replicates.
2014-06-15 | E-GEOD-54023 | biostudies-arrayexpress
Project description:Prophase I of male meiosis involves dynamic chromosome segregation processes during early spermatogenesis, including synapsis, meiotic recombination, and cohesion. Genetic defects in genes participating in these processes consistently cause reproduction failure in mice. To identify candidate genes responsible for infertility in humans, we performed expression profiling of mouse spermatogenic cells undergoing meiotic prophase I. Cell fractions enriched in spermatogonia, leptotene/zygotene spermatocytes, or pachytene spermatocytes were separately isolated from mouse testes for RNA extraction. To minimize the contamination of other cell types, we fractionated the testicular cells undergoing the first round of spermatogenesis using Percoll gradient procedure. The cell fractions were characterized by morphological analysis by phase contrast microscopy and Nomarski interference microscopy, and then expression of cell lineage- and spermatogenesis stage-specific genes were examined by RT-PCR. The most enriched fractions for spermatogonia (fraction2 from day8), leptotene/zygotene spermatocytes (fraction5 from day12), and pachytene spermatocytes (fraction8 from day15) were subjected to hybridization on Affymetrix microarrays.
2010-03-31 | E-GEOD-19532 | biostudies-arrayexpress
Project description:To understand the etiology behind higher incidence of infertility in crossbred bulls, we performed transcriptomic analysis of testicular samples derived from crossbred males and compared with testicular transcriptomic profile of Zebu cattle
2020-07-08 | GSE153952 | GEO
Project description:Infertility is a widespread health problem, with rising incidence worldwide. Whether the infertility is caused by genetic or environmental factors, the reason for inability to reproduce can be the too low number of sperm or morphological or functional abnormality of the sperm. Therefore there can be a certain possibility that divergent causes would converge in common mechanisms impairing sperm functionality. A key step in the control of the cell phenotype is the regulation of gene expression. Therefore, the sperm transcriptome can reflect the impairment of proper regulatory networks acting during spermatogenesis and later, during sperm maturation. Also, it can be speculated that some sperm RNAs can influence the fitness of the early embryo, despite the small amount of sperm RNA. Although the changes in transcriptome are not always reflected by similar changes in the proteome, a relative ease of transcriptome interrogation makes it an excellent tool for hypothesis generation about infertility mechanisms and for a search for potential infertility biomarkers.
2021-11-03 | GSE160749 | GEO
Project description:The project aimed to compare testicular proteomes from patients with obstructive and non-obstructive azoospermia in order to identify molecular signatures involved in spermatogenesis as well to identify candidate biomarkers for discriminating between different types of azoospermia. The samples used in this study were formalin fixed paraffin embedded (FFPE) testicular tissues obtained by biopsy from men with clinical diagnosis of azoospermia. Samples were grouped according to the histopathological report in 3 groups: 1) Spermatogenesis (obstructive azoospermia), 2) Hypospermatogenesis and 3) Sertoli cell only syndrome (SCO). Patients were aged 31–46 years with no differences among groups regarding age (Median age (Hypospermatogenesis) =35; Median age (SCO) =34 and Median age (Spermatogenesis) =39). Each group had 9 samples or 27 samples in total were used for the comparative proteomics analysis by label-free data-independent LC-MS/MS.
2022-07-31 | PXD032722 | Pride
Project description:We analyzed gene expression profiles of human testicular biopsies in men with idiopathic nonobstructive azoospermia. Using new generation oligonucleotide microarray platform GeneChipM-BM-. Human Gene 1.0 ST, we identified genes which could be potential biomarkers of azoospermia and molecular indicators that could determine a particular stage of impaired spermatogenesis. Thus, we shed light on genes which were had so far been weakly characterized and which were had never related to infertility before. These studies also included the comparative analysis of the hierarchical clustering of gene expression profile with histopathological data provided for azoospermic patients. We analyzed 31 testicular biopsy samples with Affymetrix Human Gene 1.0 ST microarrays. 27 of them were obtained from patients with various types of NOA and 4 with normal spermatogenesis.
2013-09-16 | E-GEOD-45885 | biostudies-arrayexpress
Project description:Male infertility is one of the most common complications of diabetes mellitus (DM). Dapagliflozin is widely used to manage the type II DM. This study aimed to assess the dapagliflozin’s effects on the spermatogenesis by administering either dapagliflozin (Dapa) or a vehicle (db) to diabetic male db/db mice, and using littermate male db/m mice as the control group (Con). We further performed the integrative analyses of the cecal shotgun metagenomics, cecal/plasmatic/testicular metabolomics, and testicular proteomics. We found that dapagliflozin treatment significantly alleviated the diabetes-induced spermatogenic dysfunction by improving sperm quality, including the sperm concentration and the sperm motility. The overall microbial composition was reshaped in Dapa mice and 13 species (such as Lachnospiraceae bacterium 3-1) were regarded as potential beneficial bacteria. Metabolites exhibited modified profiles, in which adenosine, cAMP, and 2’-deoxyinosine being notably altered in the cecum, plasma, and testis, respectively. Testicular protein expression patterns were similar between the Dapa and Con mice. In vivo results indicated that compared with db group, dapagliflozin treatment alleviated apoptosis and oxidative stress in testis tissues by down-regulating 2’-deoxyinosine. This was further validated by in vitro experiments using GC-2 cells. Our findings support the potential use of Dapa to prevent the diabetes-induced impaired sperm quality and to treat diabetic male infertility.
2024-01-04 | PXD034622 | Pride
Project description:Spermatogenesis is a complex cell differentiation process that includes marked genetic, cellular functional and structural changes. It requires tight regulation, since disturbances in any of the spermatogenic stages would lead to fertility deficiencies. In order to increase our knowledge of signal transduction during sperm development, we carried out a large-scale identification of the phosphorylation events that occur in the human gonad. Metal oxide affinity chromatography using TiOx combined with LC-MS/MS was conducted to profile the phosphoproteome of human testes with full spermatogenesis. A total of 8187 phosphopeptides derived from 2661 proteins were identified, resulting in the most complete report of human testicular phosphoproteins to date. Phosphorylation events were enriched in proteins functionally related to spermatogenesis, as well as to highly active processes in the male gonad, such as transcriptional and translational regulation, cytoskeleton organization, DNA packaging, cell cycle and apoptosis. Moreover, 174 phosphorylated kinases were identified. The most active and abundant human protein kinases in the testis were predicted both by the phosphorylation status of the kinase activation loop and the number of phosphopeptide spectra identified. The potential function of two of those kinases, cyclin-dependent kinase 12 (CDK12) and p21-activated kinase 4(PAK4), has been explored by protein-protein interaction analysis, immunodetection in human and mouse testicular tissue, and functional assay in a human embryonal carcinoma cell line. The co-localization of CDK12 with Golgi markers and probably pro-acrosomal vesicles suggests a potential crucial role of this protein kinase in sperm formation. PAK4 expression has been found limited to human spermatogonia, and a role in embryonal carcinoma cell response to apoptosis has been observed. Together, our data confirm that phosphoregulation by protein kinases is highly active in sperm differentiation, and open a window to detailed characterization and validation of potential targets for the development of drugs modulating male fertility, and tumor behavior.
2019-02-01 | PXD010246 | Pride
Project description:Despite the high incidence of male infertility, about 70% of infertile men do not receive a causative diagnosis. To gain insights into the regulatory mechanisms governing human germ cell function in normal and impaired spermatogenesis (crypto group), we combined single cell RNA sequencing (>30.000 cells), proteome, and histomorphometric analyses of testicular tissues. We found major alterations in the crypto spermatogonial compartment with increased numbers of the most undifferentiated spermatogonia (PIWIL4+ State 0 cells). We also observed a transcriptional switch within the spermatogonial compartment driven by the increased and prolonged expression of the transcription factor EGR4. Intriguingly, EGR4-regulated genes included the chromatin-associated transcriptional repressor UTF1, which was downregulated. Histomorphometrical analyses showed that these transcriptional changes were mirrored at the protein level and accompanied by a change in the chromatin structure of spermatogonia. This resulted in a reduction of Adark spermatogonia - characterized by tightly compacted chromatin and serving as reserve stem cells. These findings suggest that crypto patients are at a disadvantage especially in cases of gonadotoxic damage as they have less cells to help repopulate the testis. We hypothesize that the more relaxed chromatin status of spermatogonia is dependent on decreased UTF1 expression caused by EGR4 activation. These identified regulators of the spermatogonial compartment will be highly interesting targets to uncover genetic causes of male infertility.
2021-11-02 | PXD023979 | Pride