دورية أكاديمية
Defect in the nuclear pore membrane glycoprotein 210-like gene is associated with extreme uncondensed sperm nuclear chromatin and male infertility: a case report
| العنوان: | Defect in the nuclear pore membrane glycoprotein 210-like gene is associated with extreme uncondensed sperm nuclear chromatin and male infertility: a case report |
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| المؤلفون: | Arafah, Karim, Lopez, Fabrice, Cazin, Caroline, Kherraf, Zine‐eddine, Tassistro, Virginie, Loundou, Anderson, Arnoult, Christophe, Thierry-Mieg, Nicolas, Bulet, Philippe, Guichaoua, Marie Roberte, Ray, Pierre F |
| المساهمون: | Plateforme Biopark d'Archamps, Theories and Approaches of Genomic Complexity (TAGC), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire CHU Grenoble (CHUGA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Institut méditerranéen de biodiversité et d'écologie marine et continentale (IMBE), Avignon Université (AU)-Aix Marseille Université (AMU)-Institut de recherche pour le développement IRD : UMR237-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU), Biologie Computationnelle et Modélisation (TIMC-BCM ), Translational Innovation in Medicine and Complexity / Recherche Translationnelle et Innovation en Médecine et Complexité - UMR 5525 (TIMC ), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA) |
| المصدر: | ISSN: 0268-1161. |
| بيانات النشر: | HAL CCSD Oxford University Press (OUP) |
| سنة النشر: | 2021 |
| المجموعة: | Université Grenoble Alpes: HAL |
| مصطلحات موضوعية: | Proteomics, Exome sequencing, NUP210L, Spermatogenesis, Chromatin remodeling, Uncondensed sperm nucleus, Male infertility, MESH: Animals, MESH: Chromatin, MESH: Humans, MESH: Infertility, MESH: Male, MESH: Membrane Glycoproteins, MESH: Mice, MESH: Nuclear Pore, MESH: Spermatogenesis, MESH: Spermatozoa, [SDV.BDD.GAM]Life Sciences [q-bio]/Development Biology/Gametogenesis, [SDV.BDLR.RS]Life Sciences [q-bio]/Reproductive Biology/Sexual reproduction |
| الوصف: | International audience ; After the two meiotic divisions, haploid round spermatids undergo dramatic changes to become mature spermatozoa. One of the main transformations consists of compacting the cell nucleus to confer the sperm its remarkable hydrodynamic property and to protect its DNA from the oxidative stress it will encounter during its reproductivejourney.Here, we studied an infertile subject with low sperm count, poor motility and highly abnormal spermatozoa with strikingly large heads due to highly uncondensed nuclear sperm DNA. Whole exome sequencing was performed on the subject’s DNA to identify the genetic defect responsible for this severe sperm anomaly.Bioinformatics analysis of exome sequence data uncovered a single candidate variant: a homozygous loss of function variant, ENST00000368559.7:c.718-1G>A, altering a consensus splice site expected to prevent the synthesis of the NUP210L protein. High-resolution mass spectrometry of sperm protein extracts did not reveal any NUP210L peptide sequence in the patient’s sperm, contrary to what was observed in control donors, thus confirming the absence of NUP210L in the patient’s sperm.Interestingly, homozygous Nup210l knock-out mice have been shown to be infertile due to a reduced sperm count, a high proportion of round-headed sperm, other head and flagella defects and a poor motility.NUP210L is almost exclusively expressed in the testis and sequence analogy suggests that it encodes a nuclear pore membrane glycoprotein. The protein might be crucial to regulate nuclear trafficking during and/or before spermiogenesis, its absencepotentially impeding adequate nuclear compaction by preventing the entry of histone variants/transition proteins/protamines into the nucleus and/or by preventing the adequate replacement of core histones.This work describes a new gene necessary for male fertility, potentially improving the efficiency of the genetic diagnosis of male infertility.The function of NUP210L still remains to be resolved and its future investigation will ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/33332558; hal-02985525; https://hal.science/hal-02985525Test; https://hal.science/hal-02985525/documentTest; https://hal.science/hal-02985525/file/Arafah%202020.pdfTest; PUBMED: 33332558 |
| DOI: | 10.1093/humrep/deaa329 |
| الإتاحة: | https://doi.org/10.1093/humrep/deaa329Test https://hal.science/hal-02985525Test https://hal.science/hal-02985525/documentTest https://hal.science/hal-02985525/file/Arafah%202020.pdfTest |
| حقوق: | http://hal.archives-ouvertes.fr/licences/copyrightTest/ ; info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.A1427DF3 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1093/humrep/deaa329 |
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