Aging, inflammation and DNA damage in the somatic testicular niche with idiopathic germ cell aplasia
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA646622 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12234210_1.fastq.gz | Fastqsanger.gz | |||
| SRR12234210_2.fastq.gz | Fastqsanger.gz | |||
| SRR12234211_1.fastq.gz | Fastqsanger.gz | |||
| SRR12234211_2.fastq.gz | Fastqsanger.gz | |||
| SRR12234212_1.fastq.gz | Fastqsanger.gz |
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Project description:Germ cell aplasia represents the most severe form of male infertility, and is associated with increased risk of early onset age-related chronic diseases and higher risk of death. Here we investigated the transcriptional landscape of 3880 somatic cells clustered in Sertoli, peritubular Myoid, Leydig, endothelial, stromal, T cells and macrophages from 3 human testis with idiopathic germ cell aplasia. Deregulated somatic pathways were associated with over-expression of paternally imprinted genes in immature Leydig cells, extracellular matrix composition and organization, hormonal milieu, chronic pro-inflammatory environments and early ageing, which were validated with an external cohort of 44 men with idiopathic germ cell aplasia compared to 102 age-matched fertile men. These 7 transcriptomic datasets unveil new insights into the germ cell aplasia, and prompts new thinking to better understand the pathogenesis of the idiopathic disease and the associated clinical manifestations of early ageing process.
2021-08-04 | GSE154535 | GEO
Project description:The somatic microenvironment supports spermatogonial stem cell differentiation into sperm. Extracellular matrix (ECM) plays multiple roles in the stem cell niche, including self-renewal, proliferation, differentiation and survival of spermatogonial cells. The pathophysiology of male infertility might be representative of a progressive degenerative process of the testicular tissue, including ECM, rather than a defective genetic background, thus outlining the existence of chronic etiological agents/pathways. In this context, we sought to identify potential causative factors responsible for a number of modifications of the testicular somatic microenvironment associated with idiopathic germ cell aplasia in human beings. Proteomic analysis of the decellularized ECM was performed to study testis parenchyma from 10 idiopathic non-obstructive azoospermic (iNOA) men, dichotomized according to positive sperm retrieval versus germ cell aplasia. Germ cell aplasia was characterized by an increased nuclear distribution of the retinoic acid receptor in Sertoli cells which was associated with decreased expression of the ECM markers, Nidogen-2 and Heparan sulfate proteoglycan-2. Decreased levels of the interstitial matrisome associated Factor IX and its regulator VKORC1 were instead coupled with decreased signaling of vitamin K in Leydig cells. This study identified pathogenetic signature of the somatic testicular microenvironment and provide mechanistic insights into the molecular determinants of human idiopathic germ cell aplasia.
2019-01-07 | PXD011817 | Pride
Project description:Molecular mechanisms associated with human germ cell aplasia in infertile men remain undefined. Here we perform single-cell transcriptome profiling to highlight differentially expressed genes and pathways in each somatic cell type in testes of men with idiopathic germ cell aplasia. We identify immaturity of Leydig cells, chronic tissue inflammation, fibrosis, and senescence phenotype of the somatic cells, as well markers of chronic inflammation in the blood. We find that deregulated expression of parentally imprinted genes in myoid and immature Leydig cells, with relevant changes in the ratio of Lamin A/C transcripts and an active DNA damage response in Leydig and peritubular myoid cells are also indicative of senescence of the testicular niche. This study offers molecular insights into the pathogenesis of idiopathic germ cell aplasia.
| S-EPMC8410861 | biostudies-literature
Project description:Purpose: To understand the overall transcriptional profile changes in porcine testicular niche cells development.
2022-04-20 | GSE186479 | GEO
Project description:Pro-spermatogonia (SG) serve as the gateway to spermatogenesis. Using single-cell RNA sequencing (RNAseq), we studied the development of ProSG, their SG descendants, and testicular somatic cells, during the perinatal period in mice. We identified both gene and protein markers for 3 temporally distinct ProSG cell subsets, including a migratory cell population with a distinct transcriptome from the previously defined T1- and T2-ProSG stages. This intermediate (I)-ProSG subset translocates from the center of seminiferous tubules to the spermatogonial stem cell (SSC) “niche” in its periphery soon after birth. We identified 3 undifferentiated SG subsets at postnatal day 7, each of which express distinct genes, including transcription factor and signaling genes. Two of these subsets have the characteristics of newly emergent SSCs. We also molecularly defined the development of Sertoli, Leydig, and peritubular myoid cells during the perinatal period, allowing us to identify candidate signaling pathways acting between somatic and germ cells in a stage-specific manner during the perinatal period. Our study provides a rich resource for those investigating testicular germ and somatic cell developmental during the perinatal period.
2020-01-22 | GSE130593 | GEO
Project description:Single-cell RNA sequencing reveals testicular niche cells development in pigs
| PRJNA774048 | ENA
Project description:Testicular germ cell tumors are comprised of two histologic groups, seminomas and non-seminomas. We postulated that the possible divergent pathogeneses of these histologies may be partially explained by variable levels of net endogenous DNA damage. To test our hypothesis, we conducted a case-case analysis of 51 seminoma and 61 non-seminoma patients using data and specimens from the Familial Testicular Cancer study and the U.S. Radiologic Technologists cohort. A lymphoblastoid cell line was cultured for each patient and the alkaline comet assay was used to determine four parameters: tail DNA, tail length, comet distributed moment (CDM) and Olive tail moment (OTM). Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using logistic regression. Values for tail length, tail DNA, CDM and OTM were modelled as categorical variables using the 50th and 75th percentiles of the seminoma group. Tail DNA was significantly associated with non-seminoma compared with seminoma (OR(50th percentile) = 3.31, 95% CI: 1.00, 10.98; OR(75th percentile) = 3.71, 95% CI: 1.04, 13.20; p for trend = 0.039). OTM exhibited similar, albeit statistically non-significant, risk estimates (OR(50th percentile) = 2.27, 95% CI: 0.75, 6.87; OR(75th percentile) = 2.40, 95% CI: 0.75, 7.71; p for trend = 0.12) whereas tail length and CDM showed no association. In conclusion, the results for tail DNA and OTM indicate that net endogenous levels are higher in patients who develop non-seminoma compared with seminoma. This may partly explain the more aggressive biology and younger age-of-onset of this histologic subgroup compared with the relatively less aggressive, later-onset seminoma.
| S-EPMC2874631 | biostudies-literature
Project description:Somatic mutations of the KIT gene have been reported in mast cell diseases and gastrointestinal stromal tumours. Recently, they have also been found in mediastinal and testicular germ cell tumours (TGCTs), particularly in cases with bilateral disease. We screened the KIT coding sequence (except exon 1) for germline mutations in 240 pedigrees with two or more cases of TGCT. No germline mutations were found. Exons 10, 11 and 17 of KIT were examined for somatic mutations in 123 TGCT from 93 multiple-case testicular cancer families. Five somatic mutations were identified; four were missense amino-acid substitutions in exon 17 and one was a 12 bp in-frame deletion in exon 11. Two of seven TGCT from cases with bilateral disease carried KIT mutations compared with three out of 116 unilateral cases (P=0.026). The results indicate that somatic KIT mutations are implicated in the development of a minority of familial as well as sporadic TGCT. They also lend support to the hypothesis that KIT mutations primarily take place during embryogenesis such that primordial germ cells with KIT mutations are distributed to both testes.
| S-EPMC2410291 | biostudies-literature
Project description:Normal, premalignant and various histological subtypes of testicular germ cell tumor (TGCT) tissues were hybridized against Universal Human Reference RNA (Stratagene) onto Agilent 60mer oligo microarrays (GEO accession no GPL885). In vitro time series of two TGCT cell lines, NTERA2 and 2102Ep, treated with retinoic acid for 0, 3, and 7 days were also included. The data set (30 hybridizations) is particularly useful for comparisons between various histological subtypes of TGCT versus each other or versus normal testis. Keywords = 2102Ep Keywords = Agilent oligo microarrays Keywords = carcinoma in situ Keywords = choriocarcinoma Keywords = development Keywords = developmental biology Keywords = differenciation Keywords = embryogenesis Keywords = embryonal carcinoma Keywords = homo sapiens Keywords = human Keywords = human development Keywords = intratubular germ cell tumor Keywords = nonseminoma Keywords = NTera2 Keywords = pluripotency Keywords = pluripotent Keywords = retinoic acid Keywords = seminoma Keywords = teratocarcinoma Keywords = teratoma Keywords = testis Keywords = testicular germ cell tumor Keywords = testicular neoplasm Keywords = totipotency Keywords = totipotent Keywords = undifferentiated Keywords = universal human reference RNA (Stratagene) Keywords = yolk sac tumor Keywords: other
2005-07-01 | GSE1818 | GEO
Project description:Smooth-muscle-like peritubular cells make up the wall of semniferous tubules of men. These human testicular peritubular cells (HTPC) have been shown to fulfill different roles. They transport sperm, secrete various factors like GDNF (glial cell line derived neurotrophic factor) and are immunologically active. They might contribute to spermatogonial stem cell niche altering and testicular ageing. Previous studies were limited regarding heterogeneity (due to lifestyle, age, medical history etc.) and accessibility of HTPCs. To circumvent this problem a cellular primate model should be established. The proteome of 6 MKTPCs of individual healthy and young (2 or 3 years) donors was assessed to investigate the suitability as a model.
2018-06-06 | PXD009394 | Pride