Deficiency of the Tbc1d21 gene causes male infertility with morphological abnormalities of the sperm mitochondria and flagellum in mice
Autoři:
Ya-Yun Wang aff001; Chih-Chun Ke aff002; Yen-Lin Chen aff004; Yu-Hua Lin aff006; I-Shing Yu aff008; Wei-Chi Ku aff005; Moira K. O’Bryan aff009; Ying-Hung Lin aff001
Působiště autorů:
Graduate Institute of Biomedical and Pharmaceutical Science, Fu Jen Catholic University, New Taipei City, Taiwan
aff001; PhD Program in Nutrition & Food science, Fu Jen Catholic University, New Taipei City, Taiwan
aff002; Department of Urology, En Chu Kong Hospital, New Taipei City, Taiwan
aff003; Department of Pathology, Cardinal Tien Hospital, New Taipei City, Taiwan
aff004; School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan
aff005; Division of Urology, Department of Surgery, Cardinal Tien Hospital, New Taipei City, Taiwan
aff006; Department of Chemistry, Fu Jen Catholic University, New Taipei City, Taiwan
aff007; Laboratory Animal Center, College of Medicine, National Taiwan University, Taipei, Taiwan
aff008; School of Biological Sciences, Monash University, Melbourne, Victoria, Australia
aff009
Vyšlo v časopise:
Deficiency of the Tbc1d21 gene causes male infertility with morphological abnormalities of the sperm mitochondria and flagellum in mice. PLoS Genet 16(9): e32767. doi:10.1371/journal.pgen.1009020
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pgen.1009020
Souhrn
Approximately 2–15% of couples experience infertility, and around half of these cases are attributed to male infertility. We previously identified TBC1D21 as a sterility-related RabGAP gene derived from infertile men. However, the in vivo function of TBC1D21 in male fertility remains unclear. Here, we show that loss of Tbc1d21 in mice resulted in male infertility, characterized by defects in sperm tail structure and diminished sperm motility. The mitochondria of the sperm-tail had an abnormal irregular arrangement, abnormal diameter, and structural defects. Moreover, the axoneme structure of sperm tails was severely disturbed. Several TBC1D21 interactors were selected via proteomic analysis and functional grouping. Two of the candidate interactors, a subunit protein of translocase in the outer membrane of mitochondria (TOMM20) and an inner arm component of the sperm tail axoneme (Dynein Heavy chain 7, DNAH7), confirmed in vivo physical co-localization with TBC1D21. In addition, TOMM20 and DNAH7 detached and dispersed outside the axoneme in Tbc1d21-deficient sperm, instead of aligning with the axoneme. From a clinical perspective, the transcript levels of TBC1D21 in sperm from teratozoospermia cases were significantly reduced when compared with those in normozoospermia. We concluded that TBC1D21 is critical for mitochondrial and axoneme development of mammalian sperm.
Klíčová slova:
Epididymis – Genetically modified animals – Male infertility – Mitochondria – Mouse models – Outer membrane proteins – Sperm – Tails
Zdroje
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