Cpne1 deficiency preserves sperm motility under Ca 2+ channel blockade

• Published in: The Journal of reproduction and development Vol. 70; no. 5; p. 309
• Main Authors: Xie, Qiang, Zhang, Hanbin, Zhuang, Yuge, Liu, Jinsheng, Huang, Zicong, Zhang, Xiaoyuan, Ma, Ke, Liu, Wenyuan, Xie, Minyu, Huang, Chuyu, Zhong, Xiaojing, Chen, Feilong, Zou, Feng, Zhang, Wansong, Qiu, Chunming, Sun, Canbiao, Kang, Xiangjin, Chen, Zhenguo, Zhang, Guofei
• Format: Journal Article
• Language: English
• Published: Japan 01.10.2024
• Subjects: Animals; Azoospermia - genetics; Azoospermia - metabolism; Calcium - metabolism; Calcium Channel Blockers - pharmacology; Calcium Signaling - drug effects; Humans; Male; Mice; Mice, Knockout; Phospholipid Transfer Proteins - genetics; Phospholipid Transfer Proteins - metabolism; Sperm Motility - drug effects; Spermatogenesis - drug effects; Spermatozoa - drug effects; Spermatozoa - metabolism; Testis - drug effects; Testis - metabolism; Copine1; Sperm motility; Calcium ion; Spermatogenesis; Male infertility
• ISSN: 1348-4400
• DOI: 10.1262/jrd.2024-027

Calcium ions (Ca ) play crucial roles in sperm motility and fertilization. The copine (CPNE) family comprises several Ca -dependent phospholipid-binding proteins. Of these, CPNE1 is extensively expressed in mammalian tissues; however, its precise role in testicular development and spermatogenesis is yet to be fully characterized. In this study, we used proteomics to analyze testicular biopsies and found that levels of CPNE1 were significantly reduced in patients with non-obstructive azoospermia (defective spermatogenesis) compared to those in patients with obstructive azoospermia (physiological spermatogenesis). In mice, CPNE1 is expressed at various stages of germ cell development and is associated with the Golgi apparatus. Ultimately, CPNE1 is expressed in the flagella of mature sperms. To further examine the role of CPNE1, we developed a Cpne1 knockout mouse model. Analysis showed that the loss of Cpne1 did not impair testicular development, spermatogenesis, or sperm morphology and motility in physiological conditions. When treated with gadolinium (III) chloride or 2-aminoethoxydiphenyl borate, known inhibitors of store-operated Ca entry, Ca signals and sperm motility were significantly compromised in wild-type mice; however, both mechanisms were conserved in KO mice. These results suggested that CPNE1 is dispensable for testicular development, spermatogenesis or sperm motility in physiological conditions. In addition, CPNE1 may represent a target of Ca channel inhibitors and may therefore be implicated in the regulation of Ca signaling and sperm motility.