It is said that approximately half of infertility cases are caused by factors on the male side. There is an expectation that clarifying the molecular mechanisms of sperm fertilization inside the body will help to solve these problems.
A research team led by Associate Professor Taichi Noda and Graduate Student Reika Uriu of the Institute of Resource Development and Analysis at Kumamoto University, along with Professor Masahito Ikawa of the Research Institute for Microbial Diseases at the University of Osaka, discovered the mechanism by which male mice lacking (knockout: KO) the sperm protein GALNTL5 become nearly infertile. When observing sperm behavior in the female reproductive tract after mating, the researchers found that KO sperm were present in the uterus but rare in the oviduct and struggled to bind to the uterotubal junction (UTJ). These results showed that KO male mice become nearly infertile because the sperm cannot migrate to the oviduct and meet the eggs. Additionally, when KO sperm were cultured with eggs in vitro, the sperm could barely bind to the zona pellucida, the glycoprotein layer surrounding the egg. Approximately 30 genes expressed in male reproductive tissues are involved in sperm UTJ binding/migration and zona pellucida binding. Since GALNTL5 disappears in sperm from KO mice lacking these genes, GALNTL5 is considered the most important factor in sperm UTJ binding/migration and zona pellucida binding. Furthermore, the researchers revealed that sperm can bind to the UTJ and zona pellucida through the interaction of GALNTL5 with N-acetylgalactosamine (GalNAc) in the sugar chains present on the UTJ and zona pellucida.
This finding shows that GALNTL5 could become a new target for diagnosis and testing as a causative gene for male infertility. It is also expected to lead to the development of new contraceptives.
(Article: Masanori Nakajo)
