Kuribayashi Sohei, Fukuhara Shinichiro, Kitakaze Hiroaki, Tsujimura Go, Imanaka Takahiro, Ueda Norichika, Takezawa Kentaro, Ikawa Masahito, Nonomura Norio
Department of Urology, Osaka University Graduate School of Medicine, Suita, 565-0871, Osaka, Japan.
Research Institute for Microbial Diseases, Osaka University, Suita, 565-0871, Osaka, Japan.
Sci Rep. 2024 Dec 28;14(1):30692. doi: 10.1038/s41598-024-77986-3.
One in five couples who wish to conceive is infertile, and half of these couples have male infertility. However, the causes of male infertility are still largely unknown. Creatine is stored in the body as an energy buffer, and the testes are its second-largest reservoir after muscles. Further, even though intratesticular creatine levels have long been known to decrease in male patients with infertility, its role in the testis is unknown. We investigated the intratesticular role of creatine, specifically in the context of the creatine synthesizing enzyme Gamt, and the creatine transporter Slc6a8. The Slc6a8 knockout mice showed no abnormalities in spermatogenesis. While Gamt knockout mice formed spermatozoa, they demonstrated reduced sperm count and decreased sperm motility and fertilization rate. Additionally, intratesticular creatine in Gamt knockout mice was significantly decreased, resulting in the disruption of tight junctions, which could be rectified by creatine supplementation, as was evidenced by the improved sperm count and fertilization rate in these mice. In conclusion, we identified creatine as being required for the maintenance of the tight junction in the testis.
每五对希望受孕的夫妇中就有一对患有不孕症，其中一半夫妇存在男性不育问题。然而，男性不育的原因在很大程度上仍然未知。肌酸作为一种能量缓冲物质储存在体内，睾丸是继肌肉之后其第二大储存库。此外，尽管长期以来已知不育男性患者睾丸内的肌酸水平会降低，但其在睾丸中的作用尚不清楚。我们研究了肌酸在睾丸内的作用，特别是在肌酸合成酶Gamt和肌酸转运体Slc6a8的背景下。Slc6a8基因敲除小鼠的精子发生没有异常。虽然Gamt基因敲除小鼠能够形成精子，但它们的精子数量减少，精子活力和受精率降低。此外，Gamt基因敲除小鼠睾丸内的肌酸显著减少，导致紧密连接遭到破坏，而补充肌酸可以纠正这一情况，这些小鼠精子数量和受精率的提高就证明了这一点。总之，我们确定肌酸是维持睾丸紧密连接所必需的。
