Academic Journal
Phenotypic continuum and poor intracytoplasmic sperm injection intracytoplasmic sperm injection prognosis in patients harboring HENMT1 variants.
| العنوان: | Phenotypic continuum and poor intracytoplasmic sperm injection intracytoplasmic sperm injection prognosis in patients harboring HENMT1 variants. |
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| المؤلفون: | Wehbe, Zeina, Barbotin, Anne-Laure, Boursier, Angèle, Cazin, Caroline, Hograindleur, Jean‐pascal, Bidart, Marie, Fontaine, Emeline, Plouvier, Pauline, Puch, Florence, Satre, Véronique, Arnoult, Christophe, Mustapha, Selima, Fourati Ben, Zouari, Raoudha, Thierry-Mieg, Nicolas, Ray, Pierre, F, Kherraf, Zine-Eddine, Coutton, Charles, Martinez, Guillaume |
| المساهمون: | Centre Hospitalier Universitaire CHU Grenoble (CHUGA), 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), Centre Hospitalier Régional Universitaire CHU Lille (CHRU Lille), UF de Biologie de la procréation CHU Grenoble-Alpes, Laboratoire de biochimie et génétique moléculaire, Polyclinique les Jasmins Tunis, Modèles et Algorithmes pour la Génomique (TIMC-MAGe), 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), Laboratoire de Génétique Chromosomique CHU de Grenoble, ANR-19-CE17-0014,FLAGEL-OME,Aspects fondamentaux, génétiques et cliniques de l'infertilité masculine causée par des anomalies sévères des flagelles spermatiques(2019), ANR-21-CE17-0007,OLIGO-SPERM,Evaluation de l'importance des transmissions oligogéniques dans l'infertilité masculine(2021) |
| المصدر: | ISSN: 2047-2927 ; Andrology ; https://hal.science/hal-04700579 ; Andrology, In press, Online ahead of print. ⟨10.1111/andr.13730⟩. |
| بيانات النشر: | HAL CCSD Wiley |
| سنة النشر: | 2024 |
| المجموعة: | Université Grenoble Alpes: HAL |
| مصطلحات موضوعية: | azoospermia, infertility, piRNA, piwi pathway, spermatozoa, teratozoospermia, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, [SDV.BDD.GAM]Life Sciences [q-bio]/Development Biology/Gametogenesis, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology |
| الوصف: | International audience ; Background: Small RNAs interacting with PIWI (piRNAs) play a crucial role in regulating transposable elements and translation during spermatogenesis and are essential in male germ cell development. Disruptions in the piRNA pathway typically lead to severe spermatogenic defects and thus male infertility. The HENMT1 gene is a key player in piRNAs primary biogenesis and dysfunction of HENMT1 protein in meiotic and haploid germ cells resulted in the loss of piRNA methylation, piRNA instability, and TE de-repression. Henmt1-knockout mice exhibit a severe oligo-astheno-teratozoospermia (OAT) phenotype, whereas patients with HENMT1 variants display more severe azoospermia phenotypes, ranging from meiotic arrest to hypospermatogenesis. Through whole-exome sequencing (WES) of infertile patient cohorts, we identified two new patients with variants in the HENMT1 gene presenting spermatozoa in their ejcaulate, providing us the opportunity to study spermatozoa from these patients.Objectives: Investigate the spermatozoa of two patients harboring an HENMT1 variant to determine whether or not these scarce spermatozoa could be used with assisted reproductive technologies.Materials and methods: HENMT1 variants identified by WES were validated through Sanger sequencing. Comprehensive semen analysis was conducted, and sperm cells were subjected to transmission electron microscopy for structural examination, in situ hybridization for aneuploidy assessment, and aniline blue staining for DNA compaction status. Subsequently, we assessed their suitability for in vitro fertilization using intracytoplasmic sperm injection (IVF-ICSI).Results: Our investigations revealed a severe OAT phenotype similar to knockout mice, revealing altered sperm concentration, mobility, morphology, aneuploidy and nuclear compaction defects. Multiple IVF-ICSI attempts were also performed, but no live births were achieved.Discussion: We confirm the crucial role of HENMT1 in spermatogenesis and highlight a phenotypic continuum associated ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/39120570; PUBMED: 39120570 |
| DOI: | 10.1111/andr.13730 |
| الاتاحة: | https://hal.science/hal-04700579 https://hal.science/hal-04700579v1/document https://hal.science/hal-04700579v1/file/wehbe.andrology24.pdf https://doi.org/10.1111/andr.13730 |
| Rights: | http://creativecommons.org/licenses/by-nc/ ; info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.9A34C0C9 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1111/andr.13730 |
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