Lv Zheng, Sun Longjie, Chen Xuexue, Guo Peilan, Xie Xiaomei, Yao Xiaohong, Tian Shuang, Wang Chaofan, Shao Yujing, Liu Jiali
State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing 100193, China.
State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing 100193, China.
Int J Biol Macromol. 2025 Mar;293:139070. doi: 10.1016/j.ijbiomac.2024.139070. Epub 2024 Dec 26.
Infertility affects 10-12 % of couples worldwide, 50 % of which are male. Abnormal spermatogenesis is among the main causes of male infertility. We were curious about the possible role of transmembrane channel-like protein 7 (TMC7) in spermatogenesis because of its aberrant expression in several male infertility patients. In this study, we found that deletion of Tmc7, which is highly expressed during spermiogenesis, causes a human oligoasthenoteratozoospermia (OAT)-like phenotype in male mice. By histological analysis, TEM, RNA-seq and library-free data-independent acquisition mass spectrometry (DIA-MS) of TMC7-null mouse testes, we found that Tmc7 deletion caused abnormal swelling of trans-Golgi network (TGN) vesicles in elongated spermatids. Further immunofluorescence localization analysis revealed that these vesicles were defined by synaptophysin-like 1 (SYPL1). In addition, TMC7 may act as a potential chloride transport channel to regulate the size of transport vesicles. In conclusion, this study demonstrated that TMC7 is essential for male fertility and may be used as a potential protein for the identification and recognition of OAT. On the other hand, TMC7 may be a potential male contraceptive target.
全球范围内，10%-12%的夫妇受不孕症影响，其中50%是男性因素所致。精子发生异常是男性不育的主要原因之一。由于跨膜通道样蛋白7（TMC7）在一些男性不育患者中表达异常，我们对其在精子发生过程中可能发挥的作用产生了兴趣。在本研究中，我们发现，在精子形成过程中高表达的Tmc7缺失会导致雄性小鼠出现类似人类少弱畸精子症（OAT）的表型。通过对TMC7基因敲除小鼠睾丸进行组织学分析、透射电镜观察、RNA测序以及无标记数据非依赖采集质谱分析（DIA-MS），我们发现Tmc7缺失会导致长形精子细胞中反式高尔基体网络（TGN）囊泡异常肿胀。进一步的免疫荧光定位分析表明，这些囊泡由类突触素样蛋白1（SYPL1）所界定。此外，TMC7可能作为一种潜在的氯离子转运通道来调节转运囊泡的大小。总之，本研究表明TMC7对雄性生育力至关重要，可能作为识别和诊断OAT的潜在蛋白。另一方面，TMC7可能是一个潜在的男性避孕靶点。
