Loss of the importin Kpna2 causes infertility in male mice by disrupting the translocation of testis-specific transcription factors
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Elsevier
2023-07-21
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Subjects: | Molecular biology, Omics, Transcriptomics, |
Online Access: | http://hdl.handle.net/10261/334954 http://dx.doi.org/10.13039/501100004837 http://dx.doi.org/10.13039/501100011033 http://dx.doi.org/10.13039/501100000780 https://api.elsevier.com/content/abstract/scopus_id/85165642578 |
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dig-inia-es-10261-3349542024-05-14T20:46:19Z Loss of the importin Kpna2 causes infertility in male mice by disrupting the translocation of testis-specific transcription factors Navarrete-López, Paula Maroto, María Pericuesta Camacho, Eva Fernández González, Raúl Lombó, Marta Ramos Ibeas, Priscila Gutiérrez-Adán, Alfonso Ministerio de Ciencia e Innovación (España) Agencia Estatal de Investigación (España) European Commission Navarrete-López, Paula [0000-0002-7093-2191] Maroto, María [0000-0001-8738-5932] Pericuesta Camacho, Eva [0000-0001-9387-3270] Fernández González, Raúl [0000-0003-1989-2945] Lombó, Marta [0000-0002-2042-798X] Ramos Ibeas, Priscila [0000-0003-4578-0189] Gutiérrez-Adán, Alfonso [0000-0001-9893-9179] Molecular biology Omics Transcriptomics 22 Pág. Karyopherins mediate the movement between the nucleus and cytoplasm of specific proteins in diverse cellular processes. Through a loss-of-function approach, we here examine the role of Karyopherin Subunit Alpha 2 (Kpna2) in spermatogenesis. Knockout male mice exhibited reduced body size and sperm motility, increased sperm abnormalities, and led to the dysregulation of testis gene expression and ultimately to infertility. Impaired mRNA expression mainly affected clusters of genes expressed in spermatids and spermatocytes. Downregulated genes included a set of genes that participate in cell adhesion and extracellular matrix (ECM) organization. We detected both the enrichment of some transcription factors that bind to regions around transcription start sites of downregulated genes and the impaired transport of specific factors to the nucleus of spermatid cells. We propose that Kpna2 is essential in the seminiferous tubules for promoting the translocation of testis-specific transcription factors that control the expression of genes related to ECM organization. This research was supported by Grants RTI2018-093548-B-I00 and PID2021-122507OB-I00 funded by MCIN/AEI/10.13039/501100011033/and European Union “NextGenerationEU”/PRTR). P.N was supported by a pre-doctoral fellowship from the Spanish Ministry of Science and Innovation (MICINN) (PRE2019-088813), and M.L was supported by a Juan de la Cierva postdoctoral contract (FJC2019-040385-I) from the MICINN. We gratefully thank CESGA (Supercomputing Center of Galicia) for providing the necessary resources for the data processing. Peer reviewed 2023-09-12T11:04:48Z 2023-09-12T11:04:48Z 2023-07-21 artículo http://purl.org/coar/resource_type/c_6501 iScience 26(7): e107134 (2023) http://hdl.handle.net/10261/334954 10.1016/j.isci.2023.107134 2589-0042 http://dx.doi.org/10.13039/501100004837 http://dx.doi.org/10.13039/501100011033 http://dx.doi.org/10.13039/501100000780 37456838 2-s2.0-85165642578 https://api.elsevier.com/content/abstract/scopus_id/85165642578 en #PLACEHOLDER_PARENT_METADATA_VALUE# #PLACEHOLDER_PARENT_METADATA_VALUE# #PLACEHOLDER_PARENT_METADATA_VALUE# #PLACEHOLDER_PARENT_METADATA_VALUE# info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTI2018-093548-B-I00/ES/ANALISIS FUNCIONAL DE ISOFORMAS DE ARNM RELACIONADAS CON DESARROLLO EMBRIONARIO Y FERTILIDAD/ info:eu-repo/grantAgreement/AEI//PID2021-122507OB-I00 info:eu-repo/grantAgreement/MICINN//PRE2019-088813 info:eu-repo/grantAgreement/MICINN//FJC2019-040385-I Departamento de Reproducción Animal Publisher's version https://doi.org/10.1016/j.isci.2023.107134 Sí open application/pdf Elsevier |
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Molecular biology Omics Transcriptomics Molecular biology Omics Transcriptomics Navarrete-López, Paula Maroto, María Pericuesta Camacho, Eva Fernández González, Raúl Lombó, Marta Ramos Ibeas, Priscila Gutiérrez-Adán, Alfonso Loss of the importin Kpna2 causes infertility in male mice by disrupting the translocation of testis-specific transcription factors |
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22 Pág. |
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Ministerio de Ciencia e Innovación (España) |
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Ministerio de Ciencia e Innovación (España) Navarrete-López, Paula Maroto, María Pericuesta Camacho, Eva Fernández González, Raúl Lombó, Marta Ramos Ibeas, Priscila Gutiérrez-Adán, Alfonso |
format |
artículo |
topic_facet |
Molecular biology Omics Transcriptomics |
author |
Navarrete-López, Paula Maroto, María Pericuesta Camacho, Eva Fernández González, Raúl Lombó, Marta Ramos Ibeas, Priscila Gutiérrez-Adán, Alfonso |
author_sort |
Navarrete-López, Paula |
title |
Loss of the importin Kpna2 causes infertility in male mice by disrupting the translocation of testis-specific transcription factors |
title_short |
Loss of the importin Kpna2 causes infertility in male mice by disrupting the translocation of testis-specific transcription factors |
title_full |
Loss of the importin Kpna2 causes infertility in male mice by disrupting the translocation of testis-specific transcription factors |
title_fullStr |
Loss of the importin Kpna2 causes infertility in male mice by disrupting the translocation of testis-specific transcription factors |
title_full_unstemmed |
Loss of the importin Kpna2 causes infertility in male mice by disrupting the translocation of testis-specific transcription factors |
title_sort |
loss of the importin kpna2 causes infertility in male mice by disrupting the translocation of testis-specific transcription factors |
publisher |
Elsevier |
publishDate |
2023-07-21 |
url |
http://hdl.handle.net/10261/334954 http://dx.doi.org/10.13039/501100004837 http://dx.doi.org/10.13039/501100011033 http://dx.doi.org/10.13039/501100000780 https://api.elsevier.com/content/abstract/scopus_id/85165642578 |
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