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New testicular lumen protein is essential for male fertility

 


Newly generated sperm in the testis are not fully functional until they reach maturity in the epididymis, a tube that aids in sperm transport and storage. Male infertility can result from a lack of communication between the testis and epididymis, and new research has revealed the mechanism of this communication.

Dr. Martin Matsuk of Baylor College of Medicine, Dr. Masahito Igawa of Osaka University and his colleagues discover a new testicular lumen protein, NELL2, that triggers a series of events that allow sperm to mature in the epididymis and allow them to move. I was a woman.

Sperm production

Sperm travels through the epididymis, a long convoluted tube connected to the epididymis, the tube that travels from the sperm to the urethra, which is produced in the seminiferous tubules of the testis. When sperm enter the epididymis, they are not motile and cannot be fertilized. However, when passing through the epididymis, sperm are provided with a suitable environment for maturation and storage until ejaculation.

It is hypothesized that proteins released from the testes early in the process may act on the epididymis to reach the epididymis and allow sperm to mature.

To date, proteins that function via the signal lumiclin system have remained elusive. The orphan receptor tyrosine kinase ROS1, which is expressed in the first segment of the epididymis, was known to be required for its differentiation, but the testis factor controlling the differentiation of the first segment and the process of sperm maturation are also complete. Was not understood by. “

Dr. Martin Matsuk, Professor and Director of Baylor’s Drug Discovery Center

NELL2 identification

Researchers focused on NELL2, a protein factor secreted by testicular germ cells, as a possible fertilization regulator of rumicrin. “We have used innovative genome editing techniques to generate knockout mice that lack the NELL2 gene and have shown that these knockout males are infertile due to defective sperm motility,” the lead author Dr. Kiyozum explains. “Furthermore, those infertility can be rescued by germline-specific transgenes and excluded from other expression sites. Also, by showing tagged NELL2 in the epididymal lumen, it is possible to enhance rumicrin signaling. I showed you.”

The team observed that spermatogenesis normally progressed in the testes of NELL2 knockout mice, but their epididymis were as poorly differentiated as Ros1 knockout mice. After mating, neither the NELL2 knockout sperm nor the Ros1 knockout sperm enter the oviduct and are unable to fertilize the egg. Further research has shown that the Nell2 knockout epididymis is unable to process certain sperm surface proteins that are essential for male fertility.

Effects on male fertility?

To elaborate on their work, both senior authors, Ikawa and Matsuku, “discovered a complex series of events that caused confusion at any point in this rumiculin pathway to cause male infertility. Research on infertility and the development of male contraceptives. This unique transluminal communication pathway between tissues and organs seems to work elsewhere in our body.”

Source:

See journal:

Kiyozumi D., other (2020) OVCH2 mediated NELL2 mediated lumiculin signaling is required for male fertility. Science.. doi.org/10.1126/science.aay5134..

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