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Failure in sperm growth is linked to testicular cancer

4 May 2021
Appeared in BioNews 1093

Early embryonic germ cells, which fail to develop into sperm cells, may later become testicular cancer cells, a study in mice has shown.

During embryonic development, germ cells in the embryo have the ability to develop into any cell type, a state known as pluripotency. However, these cells should develop into either sperm cells or egg cells during sex determination. Researchers at the Baylor Institute of Medicine, Houston, Texas have demonstrated that errors in this process can lead to pluripotency carrying on into puberty, allowing some of these cells to become cancerous.

'Previous work from our lab and others indicated that defects in this sex-specific switch may play a central role in facilitating the initiation of testicular germ cell tumours,' said Dr Jason Heaney who led the work. He continued: 'In this study, we set out to test whether testicular germ cell tumours arise from germ cells that do not begin the sex-specific differentiation process and retain features of pluripotent cells.'

Germ cells typically lose their pluripotency ability as the embryo develops and they become able to only form sex cells. Sperm cells are formed in males and egg cells are formed in females, which is known as sex determination.

Testicular cancer is caused by testicular germ cell tumours in 95 percent of cases, which typically occurs after puberty. The formation of sperm cells during male sex determination happens at the same time cancer cells that form testicular germ cell tumours can develop.

The researchers used a strain of mouse that spontaneously develops germ cell tumours and have shown that a gene called NANOS2 is important for ensuring that embryonic germ cells form into mature sperm cells. They realised that germ cells that became cancerous in the mice's testes lacked NANOS2 and restoring the gene enabled the cells to mature, stopping them from becoming cancerous.

'NANOS2 plays a key role in the sex-specific development of embryonic germ cells by suppressing the female (egg) fate and promoting the male (sperm) fate,' Dr Heaney explained.

Publishing their findings in Development, even though it is currently unknown what role NANOS2 plays in the development of human testicular germ cell tumours, the team hope that their discovery about how NANOS2 controls cell fate during sex determination in mice will pave the way for preventing and treating testicular cancer in the future.

Dr Heaney said: 'Our work reveals changes in gene expression when germ cells transform into cancer cells that suggest alterations in metabolism and cell division, which could be used for targeted therapies.'

Link between sperm development and testicular cancer
Cosmos |  28 April 2021
Sperm development linked to testicular cancer
Baylor College of Medicine |  28 April 2021
Testicular germ cell tumors arise in the absence of sex-specific differentiation
Development |  28 April 2021
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