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Whole Exome Sequencing and In Silico Analysis of Human Sertoli in Patients with Non-Obstructive Azoospermia
Non-obstructive azoospermia (NOA) is a serious cause of male infertility. The Sertoli cell responds to androgens and takes on roles supporting spermatogenesis, which may cause infertility. This work aims to enhance the genetic diagnosis of NOA via the discovery of new and hub genes implicated in hum...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9604420/ https://www.ncbi.nlm.nih.gov/pubmed/36293429 http://dx.doi.org/10.3390/ijms232012570 |
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author | Azizi, Hossein Hashemi Karoii, Danial Skutella, Thomas |
author_facet | Azizi, Hossein Hashemi Karoii, Danial Skutella, Thomas |
author_sort | Azizi, Hossein |
collection | PubMed |
description | Non-obstructive azoospermia (NOA) is a serious cause of male infertility. The Sertoli cell responds to androgens and takes on roles supporting spermatogenesis, which may cause infertility. This work aims to enhance the genetic diagnosis of NOA via the discovery of new and hub genes implicated in human NOA and to better assess the odds of successful sperm extraction according to the individual’s genotype. Whole exome sequencing (WES) was done on three NOA patients to find key genes involved in NOA. We evaluated genome-wide transcripts (about 50,000 transcripts) by microarray between the Sertoli of non-obstructive azoospermia and normal cells. The microarray analysis of three human cases with different non-obstructive azoospermia revealed that 32 genes were upregulated, and the expressions of 113 genes were downregulated versus the normal case. For this purpose, Enrich Shiny GO, STRING, and Cytoscape online evaluations were applied to predict the functional and molecular interactions of proteins and then recognize the master pathways. The functional enrichment analysis demonstrated that the biological process (BP) terms “inositol lipid-mediated signaling”, “positive regulation of transcription by RNA polymerase II”, and “positive regulation of DNA-templated transcription” significantly changed in upregulated differentially expressed genes (DEGs). The BP investigation of downregulated DEGs highlighted “mitotic cytokinesis”, “regulation of protein-containing complex assembly”, “cytoskeleton-dependent cytokinesis”, and the “peptide metabolic process”. Overrepresented molecular function (MF) terms in upregulated DEGs included “ubiquitin-specific protease binding”, “protease binding”, “phosphatidylinositol trisphosphate phosphatase activity”, and “clathrin light chain binding”. Interestingly, the MF analysis of the downregulated DEGs revealed overexpression in “ATPase inhibitor activity”, “glutathione transferase activity”, and “ATPase regulator activity”. Our findings suggest that these genes and their interacting hub proteins could help determine the pathophysiologies of germ cell abnormalities and infertility. |
format | Online Article Text |
id | pubmed-9604420 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-96044202022-10-27 Whole Exome Sequencing and In Silico Analysis of Human Sertoli in Patients with Non-Obstructive Azoospermia Azizi, Hossein Hashemi Karoii, Danial Skutella, Thomas Int J Mol Sci Article Non-obstructive azoospermia (NOA) is a serious cause of male infertility. The Sertoli cell responds to androgens and takes on roles supporting spermatogenesis, which may cause infertility. This work aims to enhance the genetic diagnosis of NOA via the discovery of new and hub genes implicated in human NOA and to better assess the odds of successful sperm extraction according to the individual’s genotype. Whole exome sequencing (WES) was done on three NOA patients to find key genes involved in NOA. We evaluated genome-wide transcripts (about 50,000 transcripts) by microarray between the Sertoli of non-obstructive azoospermia and normal cells. The microarray analysis of three human cases with different non-obstructive azoospermia revealed that 32 genes were upregulated, and the expressions of 113 genes were downregulated versus the normal case. For this purpose, Enrich Shiny GO, STRING, and Cytoscape online evaluations were applied to predict the functional and molecular interactions of proteins and then recognize the master pathways. The functional enrichment analysis demonstrated that the biological process (BP) terms “inositol lipid-mediated signaling”, “positive regulation of transcription by RNA polymerase II”, and “positive regulation of DNA-templated transcription” significantly changed in upregulated differentially expressed genes (DEGs). The BP investigation of downregulated DEGs highlighted “mitotic cytokinesis”, “regulation of protein-containing complex assembly”, “cytoskeleton-dependent cytokinesis”, and the “peptide metabolic process”. Overrepresented molecular function (MF) terms in upregulated DEGs included “ubiquitin-specific protease binding”, “protease binding”, “phosphatidylinositol trisphosphate phosphatase activity”, and “clathrin light chain binding”. Interestingly, the MF analysis of the downregulated DEGs revealed overexpression in “ATPase inhibitor activity”, “glutathione transferase activity”, and “ATPase regulator activity”. Our findings suggest that these genes and their interacting hub proteins could help determine the pathophysiologies of germ cell abnormalities and infertility. MDPI 2022-10-20 /pmc/articles/PMC9604420/ /pubmed/36293429 http://dx.doi.org/10.3390/ijms232012570 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Azizi, Hossein Hashemi Karoii, Danial Skutella, Thomas Whole Exome Sequencing and In Silico Analysis of Human Sertoli in Patients with Non-Obstructive Azoospermia |
title | Whole Exome Sequencing and In Silico Analysis of Human Sertoli in Patients with Non-Obstructive Azoospermia |
title_full | Whole Exome Sequencing and In Silico Analysis of Human Sertoli in Patients with Non-Obstructive Azoospermia |
title_fullStr | Whole Exome Sequencing and In Silico Analysis of Human Sertoli in Patients with Non-Obstructive Azoospermia |
title_full_unstemmed | Whole Exome Sequencing and In Silico Analysis of Human Sertoli in Patients with Non-Obstructive Azoospermia |
title_short | Whole Exome Sequencing and In Silico Analysis of Human Sertoli in Patients with Non-Obstructive Azoospermia |
title_sort | whole exome sequencing and in silico analysis of human sertoli in patients with non-obstructive azoospermia |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9604420/ https://www.ncbi.nlm.nih.gov/pubmed/36293429 http://dx.doi.org/10.3390/ijms232012570 |
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