Scientists Are Getting Closer to Making Human Sperm in the Lab

Scientists have grown early-stage human sperm cells from blood-derived stem cells inside mice in a step that could help researchers better understand male infertility, though the work remains far from producing sperm capable of fertilisation.

Researchers at the University of Pennsylvania transplanted clusters of human cells beneath the kidneys of immunodeficient mice, where they survived for up to nine months and developed into immature sperm-forming cells, according to a study published this week.

The work advances efforts to recreate human sperm development in the laboratory, a process that has proven difficult because it begins before birth and depends on a complex biological environment that has been hard to replicate outside the body.

The researchers said the system could provide a platform for studying the earliest stages of sperm development, investigating unexplained male infertility and testing whether drugs affect reproductive cells.

The long-term goal of generating functional human sperm in the laboratory remains distant. Although the cells underwent key developmental changes and closely resembled their natural counterparts at the genetic level, they failed to mature into fully functional sperm.

Scientists have already succeeded in producing functional sperm and egg cells from mouse skin cells, which have been used to produce healthy offspring in rodents. Replicating that achievement in humans has proved considerably more challenging because human reproductive development differs substantially from that of mice.

The researchers began by converting human blood cells into induced pluripotent stem cells (iPSCs), which can develop into almost any cell type. They then guided the cells into becoming early germ cells, the precursors of sperm.

Previous attempts had stalled because the immature cells lacked the biological signals needed to continue developing. In earlier work, the team combined the cells with supportive cells taken from mouse testes, creating miniature testis-like structures in the laboratory. Those structures survived for only about 80 days because they lacked a blood supply.

To overcome that limitation, the researchers transplanted the tissue beneath mouse kidneys, where blood vessels allowed it to survive much longer.

Within six months, some of the transplanted human cells developed into spermatogonia, the stem cells that eventually generate sperm throughout adult life. The cells also underwent a near-complete epigenetic reset, a process that removes chemical markers from DNA and is considered essential for producing healthy reproductive cells.

Despite surviving for at least nine months, however, the cells never progressed to mature sperm.

The researchers suggested the mouse environment may lack some of the hormonal and molecular signals required for complete human sperm development and said replacing the mouse support cells with human ones could improve maturation.

The team also demonstrated similar results using monkey cells, an important step because non-human primates more closely resemble humans biologically and would likely be needed before any future reproductive applications could be tested.

The findings also revive ethical questions surrounding lab-grown reproductive cells.

Bioethicists have warned that the technology could eventually enable the large-scale creation of embryos for genetic selection or, when combined with gene-editing technologies, increase concerns over so-called designer babies. Others have raised concerns that reproductive cells could theoretically be created from someone’s skin or hair without their consent.

Regulators have begun considering those issues. Britain’s Human Fertilisation and Embryology Authority last year called for legislation explicitly addressing laboratory-grown reproductive cells, while the International Society for Stem Cell Research has urged careful oversight before any clinical use.

Private companies are also pursuing the field. Utah-based Paterna Biosciences has said it produced functional sperm from immature sperm cells collected during biopsies, while California startup Conception has reported generating early human egg cells from induced pluripotent stem cells. Neither company has yet published peer-reviewed results.

The University of Pennsylvania researchers said their work should be viewed as a research tool rather than a fertility treatment and stressed that producing functional human sperm in the laboratory remains a significant scientific challenge.

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