Deleterious genetic changes in AGTPBP1 result in teratozoospermia with sperm head and flagella defects.
AGTPBP1
genetic changes
male infertility
teratozoospermia
whole-exome sequencing
Journal
Journal of cellular and molecular medicine
ISSN: 1582-4934
Titre abrégé: J Cell Mol Med
Pays: England
ID NLM: 101083777
Informations de publication
Date de publication:
08 Nov 2023
08 Nov 2023
Historique:
revised:
23
10
2023
received:
20
04
2023
accepted:
28
10
2023
medline:
8
11
2023
pubmed:
8
11
2023
entrez:
8
11
2023
Statut:
aheadofprint
Résumé
Approximately 10%-15% of couples worldwide are infertile, and male factors account for approximately half of these cases. Teratozoospermia is a major cause of male infertility. Although various mutations have been identified in teratozoospermia, these can vary among ethnic groups. In this study, we performed whole-exome sequencing to identify genetic changes potentially causative of teratozoospermia. Out of seven genes identified, one, ATP/GTP Binding Protein 1 (AGTPBP1), was characterized, and three missense changes were identified in two patients (Affected A: p.Glu423Asp and p.Pro631Leu; Affected B: p.Arg811His). In those two cases, severe sperm head and tail defects were observed. Moreover, AGTPBP1 localization showed a fragmented pattern compared to control participants, with specific localization in the neck and annulus regions. Using murine models, we found that AGTPBP1 is localized in the manchette structure, which is essential for sperm structure formation. Additionally, in Agtpbp1-null mice, we observed sperm head and tail defects similar to those in sperm from AGTPBP1-mutated cases, along with abnormal polyglutamylation tubulin and decreasing △-2 tubulin levels. In this study, we established a link between genetic changes in AGTPBP1 and human teratozoospermia for the first time and identified the role of AGTPBP1 in deglutamination, which is crucial for sperm formation.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Cardinal Tien Hospital
ID : CTH-112A-2209
Organisme : Ministry of Science and Technology of the Republic of China
ID : MOST 109-2320-B-030-002-; MOST 110-2320-B-030-002-
Organisme : National Science and Technology Council in Taiwan
ID : NSTC 111-2320-B-030 -007-MY3
Informations de copyright
© 2023 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.
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