For a sperm produced in a man’s testes to fertilize a woman’s egg, it must first mature in a man’s epididymis. Now, an international team of researchers has discovered a new protein that “activates” sperm for fertilization, according to the journal “Science”
Scientists have identified a chain of events in which a protein secreted by the testes travels in the luminal fluid, binds to a receptor in the epididymis to induce its differentiation, and secretion of a second protein that matures the sperm and allows the sperm to mature. be mobile.
In the new study, researchers from the University of Osaka, in Japan, and the Baylor College of Medicine, in the United States, identified NELL2, a secreted protein factor that acts on the epididymis through this novel pathway to mediate maturation. of sperm.
Sperm are produced in the seminiferous tubules of the testes and travel through the epididymis, a long, contoured tube connected to the vas deferens. When sperm enter the epididymis, they are not motile and are unable to fertilize; however, as they pass through the epididymis, they receive an appropriate environment for maturation and storage until ejaculation.
It has been hypothesized that proteins released by the testes could act on the epididymis later, however, until now the proteins that work through this intriguing lumicrin signaling system have remained elusive.
Although the orphan receptor tyrosine kinase ROS1 expressed in the initial segment of the epididymis was known to be necessary for its differentiation, neither the testicular factors that regulate the initial differentiation of the segment nor the maturation process of sperm have been fully understood.
The researchers focused on NELL2, secreted by testicular germ cells, as a putative regulator of lumicrin fertility.
“Using innovative genome-editing technology, we generated knockout mice lacking the NELL2 gene and demonstrated that these males are sterile due to a defect in sperm motility,” explains Daiji Kiyozumi, lead author. Furthermore, their infertility could be recovered with a germ cell specific transgene, thus excluding other expression sites. We also illustrate lumicrin signaling by demonstrating labeled NELL2 in the epididymal lumen ”.
Developing the importance of these new studies, lead authors Masahito Ikawa and Martin M. Matzuk note: “We uncovered a complicated cascade of events in which disruption of any point on this lumicrin pathway renders a man infertile. ”.
“Our findings have important translational implications for diagnostic and therapeutic research in male infertility and the development of male contraceptives,” they say. This unique transluminal communication pathway between tissues and organs probably works elsewhere in our bodies. “
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