About one in six couples suffers from infertility, and about half of them are caused by men.However, little is known about the factors involved in sperm maturation.
This time, a group at the Institute for Microbial Diseases, Osaka University has clarified for the first time in the world the mechanism for switching on the sperm maturation mechanism.Because the testes do not have the ability to mature sperm, sperm that have just been produced in the testes do not have the ability to fertilize, but when they are sent to the epididymis through the lumen of the seminiferous tubule, it takes two weeks. It "matures" over a long period of time and gains fertility.During sexual maturation, testicular sperm cells secrete NELL2 protein, which stimulates the immature epididymis to induce differentiation in early childhood, turning on the sperm maturation mechanism.
In this study, first, gene expression analysis revealed that when NELL2 produced by sperm cells during sexual maturity is transported to the epididymis through the lumen, the ROS1 protein in the epididymis responds to the epididymis differentiation. I found it.We found that the more differentiated epididymis secretes the proteolytic enzyme OVCH2, and that sperm translocating the epididymis mature under the action of OVCH.In experiments using genetically modified mice, it was confirmed that even if either NELL2 in the testis or ROS1 in the epididymis is eliminated, the epididymis does not differentiate and sperm cannot mature, resulting in male infertility.
In addition, the inter-tissue communication system via a factor that passes through the lumen in this way is called "Lumikline", and its existence has been suggested for more than 40 years, but NELL2 is the Lumikline factor. It became clear for the first time in the world.The existence and mechanism of Lumikline, which was only a hypothesis until now, was clarified for the first time in this study, which added a new perspective for understanding various biological phenomena.
In the future, if the control mechanism of spermatogenesis by NELL2 is elucidated, it is expected that it will lead to the development of diagnostic / therapeutic agents and contraceptives for male infertility.
Paper information:[Science] NELL2-mediated lumicrine signaling through OVCH2 is required for male fertility
