Identification of novel cytoskeleton protein involved in spermatogenic cells and sertoli cells of non-obstructive azoospermia based on microarray and bioinformatics analysis

Abstract Background During mammalian spermatogenesis, the cytoskeleton system plays a significant role in morphological changes. Male infertility such as non-obstructive azoospermia (NOA) might be explained by studies of the cytoskeletal system during spermatogenesis. Methods The cytoskeleton, scaff...

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Main Authors: Danial Hashemi Karoii, Hossein Azizi, Maryam Darvari, Ali Qorbanee, Dawan Jamal Hawezy
Format: Article
Language:English
Published: BMC 2025-01-01
Series:BMC Medical Genomics
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Online Access:https://doi.org/10.1186/s12920-025-02087-7
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author Danial Hashemi Karoii
Hossein Azizi
Maryam Darvari
Ali Qorbanee
Dawan Jamal Hawezy
author_facet Danial Hashemi Karoii
Hossein Azizi
Maryam Darvari
Ali Qorbanee
Dawan Jamal Hawezy
author_sort Danial Hashemi Karoii
collection DOAJ
description Abstract Background During mammalian spermatogenesis, the cytoskeleton system plays a significant role in morphological changes. Male infertility such as non-obstructive azoospermia (NOA) might be explained by studies of the cytoskeletal system during spermatogenesis. Methods The cytoskeleton, scaffold, and actin-binding genes were analyzed by microarray and bioinformatics (771 spermatogenic cellsgenes and 774 Sertoli cell genes). To validate these findings, we cross-referenced our results with data from a single-cell genomics database. Results In the microarray analyses of three human cases with different NOA spermatogenic cells, the expression of TBL3, MAGEA8, KRTAP3-2, KRT35, VCAN, MYO19, FBLN2, SH3RF1, ACTR3B, STRC, THBS4, and CTNND2 were upregulated, while expression of NTN1, ITGA1, GJB1, CAPZA1, SEPTIN8, and GOLGA6L6 were downregulated. There was an increase in KIRREL3, TTLL9, GJA1, ASB1, and RGPD5 expression in the Sertoli cells of three human cases with NOA, whereas expression of DES, EPB41L2, KCTD13, KLHL8, TRIOBP, ECM2, DVL3, ARMC10, KIF23, SNX4, KLHL12, PACSIN2, ANLN, WDR90, STMN1, CYTSA, and LTBP3 were downregulated. A combined analysis of Gene Ontology (GO) and STRING, were used to predict proteins’ molecular interactions and then to recognize master pathways. Functional enrichment analysis showed that the biological process (BP) mitotic cytokinesis, cytoskeleton-dependent cytokinesis, and positive regulation of cell-substrate adhesion were significantly associated with differentially expressed genes (DEGs) in spermatogenic cells. Moleculare function (MF) of DEGs that were up/down regulated, it was found that tubulin bindings, gap junction channels, and tripeptide transmembrane transport were more significant in our analysis. An analysis of GO enrichment findings of Sertoli cells showed BP and MF to be common DEGs. Cell-cell junction assembly, cell-matrix adhesion, and regulation of SNARE complex assembly were significantly correlated with common DEGs for BP. In the study of MF, U3 snoRNA binding, and cadherin binding were significantly associated with common DEGs. Conclusion Our analysis, leveraging single-cell data, substantiated our findings, demonstrating significant alterations in gene expression patterns.
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spelling doaj-art-e86290deed1e44b29a9287a5361689872025-01-26T12:56:53ZengBMCBMC Medical Genomics1755-87942025-01-0118112610.1186/s12920-025-02087-7Identification of novel cytoskeleton protein involved in spermatogenic cells and sertoli cells of non-obstructive azoospermia based on microarray and bioinformatics analysisDanial Hashemi Karoii0Hossein Azizi1Maryam Darvari2Ali Qorbanee3Dawan Jamal Hawezy4Department of Cell and Molecular Biology, School of Biology, College of Science, University of TehranFaculty of Biotechnology, Amol University of Special Modern TechnologiesDepartment of Cellular and Molecular Biology, Islamic Azad UniversityDepartment of Surgery, Faculty of General of Medicine, Koya UniversityDepartment of Surgery, Faculty of General of Medicine, Koya UniversityAbstract Background During mammalian spermatogenesis, the cytoskeleton system plays a significant role in morphological changes. Male infertility such as non-obstructive azoospermia (NOA) might be explained by studies of the cytoskeletal system during spermatogenesis. Methods The cytoskeleton, scaffold, and actin-binding genes were analyzed by microarray and bioinformatics (771 spermatogenic cellsgenes and 774 Sertoli cell genes). To validate these findings, we cross-referenced our results with data from a single-cell genomics database. Results In the microarray analyses of three human cases with different NOA spermatogenic cells, the expression of TBL3, MAGEA8, KRTAP3-2, KRT35, VCAN, MYO19, FBLN2, SH3RF1, ACTR3B, STRC, THBS4, and CTNND2 were upregulated, while expression of NTN1, ITGA1, GJB1, CAPZA1, SEPTIN8, and GOLGA6L6 were downregulated. There was an increase in KIRREL3, TTLL9, GJA1, ASB1, and RGPD5 expression in the Sertoli cells of three human cases with NOA, whereas expression of DES, EPB41L2, KCTD13, KLHL8, TRIOBP, ECM2, DVL3, ARMC10, KIF23, SNX4, KLHL12, PACSIN2, ANLN, WDR90, STMN1, CYTSA, and LTBP3 were downregulated. A combined analysis of Gene Ontology (GO) and STRING, were used to predict proteins’ molecular interactions and then to recognize master pathways. Functional enrichment analysis showed that the biological process (BP) mitotic cytokinesis, cytoskeleton-dependent cytokinesis, and positive regulation of cell-substrate adhesion were significantly associated with differentially expressed genes (DEGs) in spermatogenic cells. Moleculare function (MF) of DEGs that were up/down regulated, it was found that tubulin bindings, gap junction channels, and tripeptide transmembrane transport were more significant in our analysis. An analysis of GO enrichment findings of Sertoli cells showed BP and MF to be common DEGs. Cell-cell junction assembly, cell-matrix adhesion, and regulation of SNARE complex assembly were significantly correlated with common DEGs for BP. In the study of MF, U3 snoRNA binding, and cadherin binding were significantly associated with common DEGs. Conclusion Our analysis, leveraging single-cell data, substantiated our findings, demonstrating significant alterations in gene expression patterns.https://doi.org/10.1186/s12920-025-02087-7Non-obstructive azoospermiaMicroarraySpermatogenic cellsSertoli cellCytoskeleton protein
spellingShingle Danial Hashemi Karoii
Hossein Azizi
Maryam Darvari
Ali Qorbanee
Dawan Jamal Hawezy
Identification of novel cytoskeleton protein involved in spermatogenic cells and sertoli cells of non-obstructive azoospermia based on microarray and bioinformatics analysis
BMC Medical Genomics
Non-obstructive azoospermia
Microarray
Spermatogenic cells
Sertoli cell
Cytoskeleton protein
title Identification of novel cytoskeleton protein involved in spermatogenic cells and sertoli cells of non-obstructive azoospermia based on microarray and bioinformatics analysis
title_full Identification of novel cytoskeleton protein involved in spermatogenic cells and sertoli cells of non-obstructive azoospermia based on microarray and bioinformatics analysis
title_fullStr Identification of novel cytoskeleton protein involved in spermatogenic cells and sertoli cells of non-obstructive azoospermia based on microarray and bioinformatics analysis
title_full_unstemmed Identification of novel cytoskeleton protein involved in spermatogenic cells and sertoli cells of non-obstructive azoospermia based on microarray and bioinformatics analysis
title_short Identification of novel cytoskeleton protein involved in spermatogenic cells and sertoli cells of non-obstructive azoospermia based on microarray and bioinformatics analysis
title_sort identification of novel cytoskeleton protein involved in spermatogenic cells and sertoli cells of non obstructive azoospermia based on microarray and bioinformatics analysis
topic Non-obstructive azoospermia
Microarray
Spermatogenic cells
Sertoli cell
Cytoskeleton protein
url https://doi.org/10.1186/s12920-025-02087-7
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