Sperm grown in lab can’t swim, but can fertilize, raising hope for infertility therapy
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Sperm cells are easy to take for granted. Men produce them in the millions on a daily basis. Billions go unused every month.

But nearly one-third of the 50 million couples with infertility around the world are unable to conceive because of the man’s inability to properly create sperm cells.

Now, by recreating the environment of the testicle in a Petri dish, scientists in China have succeeded in coaxing mouse stem cells to form sperm-like cells that could successfully fertilize eggs and make healthy pups. The researchers from the Chinese Academy of Sciences in Bejing, Nanjing Medical University, and elsewhere reported the findings Thursday in the journal Cell Stem Cell.

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“This is a groundbreaking paper in the field of male reproduction and infertility,” said Dr. Rebecca Sokol, an expert in reproductive medicine at the University of Southern California. If the work can be replicated with human cells and shown to be safe, it could revolutionize “the treatment of men who present with the inability to produce normal mature sperm cells.”

Reproductive biologists have spent decades trying to grow the precursors to sperm and eggs in lab dishes, using “pluripotent” stem cells as their starter ingredients.

These cells are shape-shifters. They’re found naturally in the embryo, where they divide into a whole whack of different kinds of cells in order to create all the necessary tissues to make a body. That process can also be mimicked in the lab by reprogramming skin cells to be just as malleable.

Both embryonic and reprogrammed stem cells have been used to artificially make heart cells and muscle cells, pancreatic cells, and neurons. But the gametes that allow us to reproduce have proven trickier to engineer.

Then, a few years ago researchers in Japan succeeded in nudging mouse stem cells into becoming proto-gametes. To turn them into sperm or eggs, though, the researchers needed to inject them into testicles or ovaries, where swarms of hormone-producing cells create the perfect nursery for reproductive cells.

 

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In humans, that would be out of the question: The engineered cells might lose control and create tumors. A fully lab-based protocol was needed.

To get around inserting the lab-grown cells into a real live testicle, the Chinese research team behind the new paper brought the testicle into the lab. They surgically removed the gonads of a young mouse, soaking them in enzymes to dissolve the tissue and release the cells. Then they dropped in some proto-gametes made from mouse embryonic stem cells.

Reacting to their new gonad-like environment, the cells began to develop. And because these cells had been genetically modified to glow when they produced certain proteins, the scientists were able to watch a microscopic light show of greens and purples and reds as the cells went through different stages on the path to sperm-hood.

These colors indicated that the cells were going through every step of meiosis, the process by which genetic material is split in two to form gametes. The slightest mistake could result in birth defects, such as Down syndrome.

In the end, “they didn’t make a fully mature sperm,” noted Dr. Jacob Hanna, a stem cell biologist at the Weizmann Institute of Science in Israel. “They made one step before,” he said, “which is basically like a sperm without a tail.”

Those tail-less sperm couldn’t swim their way into an egg, but they could be injected in. And the resulting mouse babies were themselves fertile.

Scientists can imagine how this might help men with fertility issues: harvest some skin cells, tweak them genetically to become induced pluripotent stem cells, coax them to form proto-gametes, and then slip these into a testicle-on-a-dish that comes either from a cadaver or a monkey. The resulting sperm-like cells, researchers hope, should be able to fertilize a human egg.

That doesn’t mean we’re anywhere near a Petri-dish cure for male infertility, though. Each of those steps will require years of research and validation to make sure they are safe.

And before any of those experiments, these mouse results will need to be replicated. “It’s a very complicated procedure, and there are always some intangibles,” said John Schimenti, a geneticist at Cornell University. “When another group does it, then people will fully believe it.”

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