Gene expression profiles of ovarian Sertoli-Leydig cell tumors
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE71160 | GEO | 2015/10/01
SECONDARY ACCESSION(S): PRJNA290478
REPOSITORIES: GEO
Similar Datasets
Project description:Background: Germline truncating mutations in DICER1, an RNase III-type endoribonuclease essential for processing of microRNAs, are seen in families with the pleuropulmonary blastoma-family tumor and dysplasia syndrome; these individuals have a propensity to develop non-epithelial ovarian tumors (i.e. sex-cord stromal and germ cell tumors). Methods: We sequenced the whole transcriptomes or exomes of 14 non-epithelial ovarian tumors and noted closely clustered mutations in the RNase IIIb domain of DICER1 in four cases. Using Sanger sequencing, we then analyzed additional ovarian tumors for mutations in this region. The impact of the mutations on the enzymatic activity of Dicer1 was determined using in vitro RNA cleavage assays. Results: RNase IIIb domain DICER1 mutations were found in 30/102 non-epithelial ovarian tumors (29%), predominantly Sertoli-Leydig cell tumors (26/43, 60%), including 4/4 from individuals with germline DICER1 mutations. The mutations were restricted to metal binding sites within the RNase IIIb catalytic centres critical for miRNA interaction and cleavage, and were somatic in all 14 cases where germline DNA was available for testing. Of 266 epithelial ovarian and endometrial cancers tested, one case, an ovarian carcinosarcoma, had a hotspot mutation. In vitro, the mutant DICER proteins showed reduced RNase IIIb activity but retained RNase IIIa activity. Conclusions: Somatic missense mutations of the RNase IIIb domain of DICER1 are common in non-epithelial ovarian tumors. Genetic, pathologic, and functional evidence suggest that these mutations do not obliterate DICER1 function, rather, they alter it in specific cell types, a novel mechanism through which perturbed microRNA expression is oncogenic.
| EGAS00001000135 | EGA
Project description:In this study, we aim to figure out if Sertoli cells released exosomes can regulate the survival and steroidogenesis of Leydig cells. We found Sertoli cells released exosomes can cross the blood-testis barrier, deliver their contents into the Leydig cells, and promote the survival of Leydig cells through CCL20.
2021-05-25 | GSE158251 | GEO
Project description:Analysis of Sertoli and Leydig cell “translatome” utilizing an in vivo ribosome tagging strategy (RiboTag) that allows a detailed and physiologically relevant characterization of the polysome-associated mRNAs in vivo. Although progress has been made in the identification of specific transcripts that are translated in Sertoli and Leydig cells and their response to hormones, efforts to expand these studies have been restricted by technical hurdles. Our analysis identified all previously characterized Leydig and Sertoli cell-specific markers and identified in a comprehensive manner novel markers of Leydig and Sertoli cells; the translational response of these two cell types to gonadotropins or testosterone was also investigated.
2013-04-06 | GSE45799 | GEO
Project description:Analysis of Sertoli and Leydig cell “translatome” utilizing an in vivo ribosome tagging strategy (RiboTag) that allows a detailed and physiologically relevant characterization of the polysome-associated mRNAs in vivo. Although progress has been made in the identification of specific transcripts that are translated in Sertoli and Leydig cells and their response to hormones, efforts to expand these studies have been restricted by technical hurdles. Our analysis identified all previously characterized Leydig and Sertoli cell-specific markers and identified in a comprehensive manner novel markers of Leydig and Sertoli cells; the translational response of these two cell types to gonadotropins or testosterone was also investigated. Leydig cell-specific (Cyp17iCre: RiboTag) and Sertoli cell-specific (AMH-Cre: RiboTag) RiboTag mice were obtained by crossing RiboTag homozygous mice with Cyp17iCre or AMH-Cre mice. For in vivo LH treatment experiments, mice were injected with the GnRH antagonist acyline for 4 days before a single injection of purified human LH. After treatment, testes were homogenized and polysomes were immunoprecipitated by utilizing an anti-HA antibody. RNA was extracted, labelled, and hybridized to Mouse Gene ST 1.0 arrays.
2013-04-06 | E-GEOD-45799 | biostudies-arrayexpress
Project description:This study was designed to investigate the toxicological effects of MEHP on TM3 Leydig and TM4 Sertoli cells.
2024-05-25 | GSE243503 | GEO
Project description:This SuperSeries is composed of the following subset Series:; GSE13237: Effect of DEHP on adult mouse Sertoli cells rich areas (SCRA); GSE13240: Effect of DEHP on adult mouse Leydig cells Experiment Overall Design: Refer to individual Series
2009-02-27 | E-GEOD-13241 | biostudies-arrayexpress
Project description:Spermatogonial stem cells are quiescent, undergo self-renewal or differentiating divisions, thereby forming the cellular basis of spermatogenesis. This cellular development is orchestrated by follicle-stimulating hormone (FSH), through the production of Sertoli cell-derived factors, and by Leydig cell-released androgens. Here, we investigate the transcriptional events induced by Fsh in a steroid-independent manner on the restart of zebrafish (Danio rerio) spermatogenesis ex vivo, using testis from adult males where type A spermatogonia were enriched by estrogen treatment in vivo. Under these conditions, RNA sequencing preferentially detected differentially expressed genes in somatic/Sertoli cells. Fsh-stimulated spermatogonial proliferation was accompanied by modulating several signaling systems (i.e. Tgf-β, Hedgehog, Wnt and Notch pathways). In silico protein-protein interaction analysis indicated a role for Hedgehog family members potentially integrating signals from different pathways during fish spermatogenesis. Moreover, Fsh had a marked impact on metabolic genes, such as lactate and fatty acid metabolism, or on Sertoli cell barrier components. Fish Leydig cells express the Fsh receptor and one of the most robust Fsh-responsive genes was insulin-like 3 (insl3), a Leydig cell-derived growth factor. Follow-up work showed that recombinant zebrafish Insl3 mediated pro-differentiation effects of Fsh on spermatogonia in an androgen-independent manner. Our experimental approach allowed focusing on testicular somatic genes in zebrafish and showed that the activity of signaling systems known to be relevant in stem cell systems was modulated by Fsh, providing promising leads for future work, as exemplified by the studies on Insl3.
2016-09-13 | GSE84436 | GEO
Project description:RNA-seq of TM3 Leydig and TM4 Sertoli cells under MEHP exposure
| PRJNA1018824 | ENA
Project description:Transcript changes in primary Leydig cells treated with Sertoli cell released exosomes
| PRJNA664588 | ENA
Project description:CONTEXT:Nontoxic multinodular goiter (MNG) is frequently observed in the general population, but little is known about the underlying genetic susceptibility to this disease. Familial cases of MNG have been reported, and published reports describe 5 families that also contain at least 1 individual with a Sertoli-Leydig cell tumor of the ovary (SLCT). Germline mutations in DICER1, a gene that codes for an RNase III endoribonuclease, have been identified in families affected by pleuropulmonary blastoma (PPB), some of whom include cases of MNG and gonadal tumors such as SLCTs. OBJECTIVE:To determine whether familial MNG with or without SLCT in the absence of PPB was associated with mutations in DICER1. DESIGN, SETTING, AND PATIENTS:From September 2009 to September 2010, we screened 53 individuals from 2 MNG and 3 MNG/SLCT families at McGill University for mutations in DICER1. We investigated blood lymphocytes and MNG and SLCT tissue from family members for loss of the wild-type DICER1 allele (loss of heterozygosity), DICER1 expression, and microRNA (miRNA) dysregulation. MAIN OUTCOME MEASURE:Detection of germline DICER1 gene mutations in familial MNG with and without SLCT. RESULTS:We identified and characterized germline DICER1 mutations in 37 individuals from 5 families. Two mutations were predicted to be protein truncating, 2 resulted in in-frame deletions, and 1 was a missense mutation. Molecular analysis of the 3 SLCTs showed no loss of heterozygosity of DICER1, and immunohistochemical analysis in 2 samples showed strong expression of DICER1 in Sertoli cells but weak staining of Leydig cells. miRNA profiling of RNA from lymphoblastoid cell lines from both affected and unaffected members of the familial MNG cases revealed miRNA perturbations in DICER1 mutation carriers. CONCLUSIONS:DICER1 mutations are associated with both familial MNG and MNG with SLCT, independent of PPB. These germline DICER1 mutations are associated with dysregulation of miRNA expression patterns.
| S-EPMC3406486 | biostudies-literature