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.
Journal of cellular and molecular medicine. 2023 Nov 08 [Epub ahead of print]
Yu-Hua Lin, Ya-Yun Wang, Tsung-Hsuan Lai, Jih-Lung Teng, Chi-Wei Lin, Chih-Chun Ke, I-Shing Yu, Hui-Ling Lee, Chying-Chyuan Chan, Chi-Hua Tung, Donald F Conrad, Moira K O'Bryan, Ying-Hung Lin
Division of Urology, Department of Surgery, Cardinal Tien Hospital, New Taipei, Taiwan., Graduate Institute of Biomedical and Pharmaceutical Science, Fu Jen Catholic University, New Taipei City, Taiwan., Department of Obstetrics and Gynecology, Cathay General Hospital, Taipei, Taiwan., Department of Urology, En Chu Kong Hospital, New Taipei City, Taiwan., Laboratory Animal Center, College of Medicine, National Taiwan University, Taipei, Taiwan., Department of Chemistry, Fu Jen Catholic University, New Taipei City, Taiwan., Department of Obstetrics and Gynecology, Taipei City Hospital, Zhongxing Branch and Branch for Women and Children, Taipei, Taiwan., Program of Artificial Intelligence & Information Security, Fu Jen Catholic University, New Taipei City, Taiwan., Division of Genetics, Oregon National Primate Research Center, Beaverton, Oregon, USA., School of BioSciences and Bio21 Institute, The University of Melbourne, Parkville, Victoria, Australia.