DEFECT IN THE NUCLEAR PORE MEMBRANE GLYCOPROTEIN 210-LIKE GENE IS ASSOCIATED WITH EXTREME SPERM NUCLEAR CHROMATIN UNCONDENSATION AND MALE INFERTILITY. - Archive ouverte HAL Accéder directement au contenu Accéder directement à la navigation
Article dans une revue

DEFECT IN THE NUCLEAR PORE MEMBRANE GLYCOPROTEIN 210-LIKE GENE IS ASSOCIATED WITH EXTREME SPERM NUCLEAR CHROMATIN UNCONDENSATION AND MALE INFERTILITY.

Abstract : 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 help to understand the complex mechanisms necessary for sperm compaction.
Liste complète des métadonnées

https://hal.archives-ouvertes.fr/hal-02985525
Contributeur : Virginie Tassistro <>
Soumis le : lundi 15 février 2021 - 12:11:49
Dernière modification le : jeudi 6 mai 2021 - 08:52:01

Fichier

 Accès restreint
Fichier visible le : 2021-06-18

Connectez-vous pour demander l'accès au fichier

Identifiants

Citation

Karim Arafah, Fabrice Lopez, Caroline Cazin, Zine‐eddine Kherraf, Virginie Tassistro, et al.. DEFECT IN THE NUCLEAR PORE MEMBRANE GLYCOPROTEIN 210-LIKE GENE IS ASSOCIATED WITH EXTREME SPERM NUCLEAR CHROMATIN UNCONDENSATION AND MALE INFERTILITY.. Human Reproduction, Oxford University Press (OUP), In press, ⟨10.1093/humrep/deaa329⟩. ⟨hal-02985525⟩

Partager

Métriques

Consultations de la notice

243