Study turns skin tissue from infertile men into early-stage sperm cells

Live sperm through a microscope. The study suggests infertile men may have lost the stem cells in their testes that usually develop into sperm. Photo: Mads Nissen/Panos

Scientists have turned skin tissue from infertile men into early-stage sperm cells in a groundbreaking study that raises hopes for new therapies for the condition.

The unexpected success of the procedure has stunned some scientists, because it was thought to be impossible for the men to make any sperm.

The men who took part in the study had major genetic defects on their Y sex chromosomes, which meant they could not produce healthy adult sperm on their own.

About 1% of men cannot make any sperm, a condition known as azoospermia, while a fifth of men have low sperm counts. Male fertility is a concern for roughly half of couples who seek IVF treatment.

In the latest study, researchers took skin cells from three infertile men and converted them into stem cells, which can grow into almost any tissue in the body. When these cells were transplanted into the testes of mice, they developed into early-stage human sperm cells.

"What we found was that cells from men who did not possess sperm at the time of clinical observation were able to produce the precursors for sperm," said Cyril Ramathal, of Stanford University.

Skin cells from infertile men grew into fewer early-stage sperm cells than cells taken from normally fertile men, the study found.

The research is at an early stage, but scientists suspect that the converted skin cells might have grown into mature sperm cells if they had been transplanted into the infertile men's testes.

If further work confirms the suspicion, it may be possible to restore male fertility by taking men's skin cells, turning them into stem cells, and injecting these into their testes. The same might be done for men who are left infertile after having chemotherapy for cancer.

"Being able to efficiently convert skin cells into sperm would allow this group to become biologic fathers," said Michael Eisenberg, director of male reproduction and surgery at Stanford, who was not involved in the study. "Infertility is one of the most common and devastating complications of cancer treatments, especially for young boys and men."

The study, published in the journal Cell Reports, suggests that rather than being unable to make healthy sperm, the men may simply have lost the population of stem cells in their testes that usually grow into sperm.

The scientists took skin cells from the men and produced batches of 1.5m induced pluripotent stem (iPS) cells to transplant into the mice. Each batch was injected into the seminiferous tubules in mouse testes, where sperm normally develop. The cells that lodged in the tubules developed into early-stage sperm cells, but others turned into small tumours. The danger of causing cancer in the men is one of the major risks that scientists need to overcome.

"It's remarkable that you can make iPS cells turn into early sperm cells in men with these genetic deletions," said Allan Pacey, senior lecturer in andrology at Sheffield University. "By the time we see them in clinic, they are not making sperm and don't have any stem cells to make them from, but that doesn't mean they didn't have them once.

"This work suggests these infertile men might have had testicular stem cells at some point, and the problem is that they cannot maintain them. So if you can make iPS cells and put them back into the man, you might be able to keep enough in the testes for them to produce some sperm. You'll never restore them back to normal, but they might have a few months or years of making sperm that's enough to give them fertility back," Pacey said.

In the UK, the use of artificially created sperm to make babies is banned. But sperm made through this technique – where converted skin cells are grown into sperm in the men's testes – may be legal to use as they are created inside the body.