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Aging, inflammation and DNA damage in the somatic testicular niche with idiopathic germ cell aplasia

ABSTRACT: Aging, inflammation and DNA damage in the somatic testicular niche with idiopathic germ cell aplasia

PROVIDER: PRJNA646622 | ENA |

REPOSITORIES: ENA

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Aging, inflammation and DNA damage in the somatic testicular niche with idiopathic germ cell aplasia

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

Aging, inflammation and DNA damage in the somatic testicular niche with idiopathic germ cell aplasia.

Project description: Not available

| S-EPMC8410861 | biostudies-literature

Protein composition of the extracellular matrix in idiopathic germ cell aplasia

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

Single-cell RNA sequencing reveals testicular niche cells development in pigs

Project description:Purpose: To understand the overall transcriptional profile changes in porcine testicular niche cells development.

2022-04-20 | GSE186479 | GEO

Single-cell RNAseq analysis of testicular germ and somatic cell development during the perinatal period

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.

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Single-cell RNA sequencing reveals testicular niche cells development in pigs

Project description:Single-cell RNA sequencing reveals testicular niche cells development in pigs

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Endogenous DNA damage and testicular germ cell tumors.

Project description: Not available

| S-EPMC2874631 | biostudies-literature

Somatic mutations of KIT in familial testicular germ cell tumours.

Project description: Not available

| S-EPMC2410291 | biostudies-literature

Testicular germ cell tumors and their histological subgroups

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

Characterization of a nonhuman primate model for the study of testicular peritubular cells – comparison with human testicular cells

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

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