Disruption of male fertility-critical Dcaf17 dysregulates mouse testis transcriptome
Abstract During mammalian spermatogenesis, the ubiquitin proteasome system maintains protein homoeostasis (proteastasis) and spermatogenic cellular functions. DCAF17 is a substrate receptor in the ubiquitin CRL4 E3 Ligase complex, absence of which causes oligoasthenoteratozoospermia in mice resultin...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-12-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-25826-7 |
| _version_ | 1828115268258234368 |
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| author | Raed Abu-Dawud Bhavesh V. Mistry Mohamed Rajab Maha Alanazi Nadya Al-Yacoub Junaid Kashir Falah Almohanna Dilek Colak Abdullah M. Assiri |
| author_facet | Raed Abu-Dawud Bhavesh V. Mistry Mohamed Rajab Maha Alanazi Nadya Al-Yacoub Junaid Kashir Falah Almohanna Dilek Colak Abdullah M. Assiri |
| author_sort | Raed Abu-Dawud |
| collection | DOAJ |
| description | Abstract During mammalian spermatogenesis, the ubiquitin proteasome system maintains protein homoeostasis (proteastasis) and spermatogenic cellular functions. DCAF17 is a substrate receptor in the ubiquitin CRL4 E3 Ligase complex, absence of which causes oligoasthenoteratozoospermia in mice resulting in male infertility. To determine the molecular phenomenon underlying the infertility phenotype caused by disrupting Dcaf17, we performed RNA-sequencing-based gene expression profiling of 3-weeks and 8-weeks old Dcaf17 wild type and Dcaf17 disrupted mutant mice testes. At three weeks, 44% and 56% differentially expressed genes (DEGs) were up- and down-regulated, respectively, with 32% and 68% DEGs were up- and down-regulated, respectively at 8 weeks. DEGs include protein coding genes and lncRNAs distributed across all autosomes and the X chromosome. Gene ontology analysis revealed major biological processes including proteolysis, regulation of transcription and chromatin remodelling are affected due to Dcaf17 disruption. We found that Dcaf17 disruption up-regulated several somatic genes, while germline-associated genes were down-regulated. Up to 10% of upregulated, and 12% of downregulated, genes were implicated in male reproductive phenotypes. Moreover, a large proportion of the up-regulated genes were highly expressed in spermatogonia and spermatocytes, while the majority of downregulated genes were predominantly expressed in round spermatids. Collectively, these data show that the Dcaf17 disruption affects directly or indirectly testicular proteastasis and transcriptional signature in mouse. |
| first_indexed | 2024-04-11T12:37:36Z |
| format | Article |
| id | doaj.art-594792049e564ec1950eaa5c3ef77cf5 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-11T12:37:36Z |
| publishDate | 2022-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-594792049e564ec1950eaa5c3ef77cf52022-12-22T04:23:35ZengNature PortfolioScientific Reports2045-23222022-12-0112111510.1038/s41598-022-25826-7Disruption of male fertility-critical Dcaf17 dysregulates mouse testis transcriptomeRaed Abu-Dawud0Bhavesh V. Mistry1Mohamed Rajab2Maha Alanazi3Nadya Al-Yacoub4Junaid Kashir5Falah Almohanna6Dilek Colak7Abdullah M. Assiri8Department of Comparative Medicine, King Faisal Specialist Hospital & Research CentreDepartment of Comparative Medicine, King Faisal Specialist Hospital & Research CentreDepartment of Comparative Medicine, King Faisal Specialist Hospital & Research CentreDepartment of Comparative Medicine, King Faisal Specialist Hospital & Research CentreDepartment of Comparative Medicine, King Faisal Specialist Hospital & Research CentreCollege of Medicine, Alfaisal UniversityDepartment of Comparative Medicine, King Faisal Specialist Hospital & Research CentreDepartment of Molecular Oncology, King Faisal Specialist Hospital & Research CentreDepartment of Comparative Medicine, King Faisal Specialist Hospital & Research CentreAbstract During mammalian spermatogenesis, the ubiquitin proteasome system maintains protein homoeostasis (proteastasis) and spermatogenic cellular functions. DCAF17 is a substrate receptor in the ubiquitin CRL4 E3 Ligase complex, absence of which causes oligoasthenoteratozoospermia in mice resulting in male infertility. To determine the molecular phenomenon underlying the infertility phenotype caused by disrupting Dcaf17, we performed RNA-sequencing-based gene expression profiling of 3-weeks and 8-weeks old Dcaf17 wild type and Dcaf17 disrupted mutant mice testes. At three weeks, 44% and 56% differentially expressed genes (DEGs) were up- and down-regulated, respectively, with 32% and 68% DEGs were up- and down-regulated, respectively at 8 weeks. DEGs include protein coding genes and lncRNAs distributed across all autosomes and the X chromosome. Gene ontology analysis revealed major biological processes including proteolysis, regulation of transcription and chromatin remodelling are affected due to Dcaf17 disruption. We found that Dcaf17 disruption up-regulated several somatic genes, while germline-associated genes were down-regulated. Up to 10% of upregulated, and 12% of downregulated, genes were implicated in male reproductive phenotypes. Moreover, a large proportion of the up-regulated genes were highly expressed in spermatogonia and spermatocytes, while the majority of downregulated genes were predominantly expressed in round spermatids. Collectively, these data show that the Dcaf17 disruption affects directly or indirectly testicular proteastasis and transcriptional signature in mouse.https://doi.org/10.1038/s41598-022-25826-7 |
| spellingShingle | Raed Abu-Dawud Bhavesh V. Mistry Mohamed Rajab Maha Alanazi Nadya Al-Yacoub Junaid Kashir Falah Almohanna Dilek Colak Abdullah M. Assiri Disruption of male fertility-critical Dcaf17 dysregulates mouse testis transcriptome Scientific Reports |
| title | Disruption of male fertility-critical Dcaf17 dysregulates mouse testis transcriptome |
| title_full | Disruption of male fertility-critical Dcaf17 dysregulates mouse testis transcriptome |
| title_fullStr | Disruption of male fertility-critical Dcaf17 dysregulates mouse testis transcriptome |
| title_full_unstemmed | Disruption of male fertility-critical Dcaf17 dysregulates mouse testis transcriptome |
| title_short | Disruption of male fertility-critical Dcaf17 dysregulates mouse testis transcriptome |
| title_sort | disruption of male fertility critical dcaf17 dysregulates mouse testis transcriptome |
| url | https://doi.org/10.1038/s41598-022-25826-7 |
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