Lab-grown sperm: scientists inch closer to fertility breakthrough

It sounds like science fiction: collecting a person’s blood cells, engineering them so they eventually transform into immature sperm, and then incubating them in a tiny pouch grown on a mouse’s kidney.

The quest to make babies with lab-grown eggs and sperm

But it’s not. Today, a team of researchers reported in the journal Cell Stem Cell¹ that it has successfully carried out the procedure, with the ultimate goal of making mature human sperm in the laboratory.

For now, that goal remains elusive. The lab-grown cells stopped developing at an immature stage. Many hurdles need to be overcome to create mature sperm in the lab, says Eoin Whelan, a reproductive biologist at the University of Pennsylvania in Philadelphia who is a member of the research team. But the latest feat is a step in the right direction.

In the meantime, the procedure could be used to study early stages of human sperm development and to hunt for reasons behind male infertility. Around 40% of male-infertility cases have no known cause. “We are approaching this from a basic science perspective,” Whelan says. “We are a long way from clinical application.”

An elusive goal

Some of the potential clinical applications are controversial, particularly the idea of using lab-grown sperm or eggs to make babies. Although some researchers hope that the approach could be used to treat specific cases of infertility, the practice also raises ethical concerns. One of these is that the technique could make it easier to genetically modify reproductive cells to produce ‘designer babies’.

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So far, a handful of researchers have been able to make mouse eggs and sperm from mouse skin cells. These cells are genetically reprogrammed so that they transform into induced pluripotent stem (iPS) cells — ‘youthful’ cells that act like those in embryos and can be chemically or genetically coaxed to turn into completely different cells, such as sperm. One team even used the approach to generate offspring from two male mice².

But researchers have not been able to translate these successes in mice to humans or other primates because of differences in how the species develop. It is also difficult to study human fetal development, so researchers aiming to understand and recapitulate the earliest days of sperm and egg development are left fumbling in the dark. “In humans, the work is so behind,” says Kotaro Sasaki, a developmental biologist also at the University of Pennsylvania.

Step by step

Sasaki and his colleagues previously determined how to convert human iPS cells into those that resemble early, embryonic cells that eventually give rise to eggs and sperm³. The researchers then mixed those immature cells with non-reproductive cells found in the testicles of developing mice⁴. The non-reproductive mouse cells can provide the protection and nutrients needed to support sperm development.

This allowed Sasaki and his colleagues to tiptoe closer to growing mature sperm, but the cells did not progress beyond the early stage of sperm development that is found in human fetuses.

Now, Sasaki, Whelan and their colleagues have taken the process further by transplanting their mixture of cells into living mice — on a region of the kidney that is known to be well-suited for supporting transplanted tissues.

Once in that pouch, the transplanted cells self-organized into tubular structures similar to those in testicles where sperm are produced. Six months after the transplant, the human cells had developed into spermatogonia, a type of cell that can eventually give rise to mature sperm.