| Autor: |
Du, Yao-qiang, Shu, Chong-yi, Zheng, Min, Xu, Wei-de, Sun, Yue, Shen, Lu, Zhang, Chen, Zhang, Yu-xin, Wang, Qian-ni, Li, Kai-qiang, Chen, Bing-yu, Hao, Ke, Lyu, Jian-xin, Wang, Zhen |
| Zdroj: |
Current Medical Science; 20230101, Issue: Preprints p1-11, 11p |
| Abstrakt: |
Objective: The protein interacting with C kinase 1 (PICK1) plays a critical role in vesicle trafficking, and its deficiency in sperm cells results in abnormal vesicle trafficking from Golgi to acrosome, which eventually disrupts acrosome formation and leads to male infertility. Methods: An azoospermia sample was filtered, and the laboratory detection and clinical phenotype indicated typical azoospermia in the patient. We sequenced all of the exons in the PICK1gene and found that there was a novel homozygous variant in the PICK1gene, c.364delA (p.Lys122SerfsX8), and this protein structure truncating variant seriously affected the biological function. Then we constructed a PICK1knockout mouse model using clustered regularly interspaced short palindromic repeat cutting technology (CRISPRc). Results: The sperm from PICK1knockout mice showed acrosome and nucleus abnormalities, as well as dysfunctional mitochondrial sheath formation. Both the total sperm and motility sperm counts were decreased in the PICK1knockout mice compared to wild-type mice. Moreover, the mitochondrial dysfunction was verified in the mice. These defects in the male PICK1knockout mice may have eventually led to complete infertility. Conclusion: The c.364delA novel variant in the PICK1gene associated with clinical infertility, and pathogenic variants in the PICK1may cause azoospermia or asthenospermia by impairing mitochondrial function in both mice and humans. |
| Databáze: |
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