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Deleterious genetic changes in AGTPBP1 result in teratozoospermia with sperm head and flagella defects.

ABSTRACT: 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.

SUBMITTER: Lin YH

PROVIDER: S-EPMC10826451 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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Deleterious genetic changes in AGTPBP1 result in teratozoospermia with sperm head and flagella defects.

Lin Yu-Hua YH Wang Ya-Yun YY Lai Tsung-Hsuan TH Teng Jih-Lung JL Lin Chi-Wei CW Ke Chih-Chun CC Yu I-Shing IS Lee Hui-Ling HL Chan Chying-Chyuan CC Tung Chi-Hua CH Conrad Donald F DF O'Bryan Moira K MK Lin Ying-Hung YH

Journal of cellular and molecular medicine 20231108 2

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 ...[more]

PMID: 37937809

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Dataset Information

Deleterious genetic changes in AGTPBP1 result in teratozoospermia with sperm head and flagella defects.

Publications

Deleterious genetic changes in AGTPBP1 result in teratozoospermia with sperm head and flagella defects.

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