Scientists are close to growing sperm in the laboratory

The research brings scientists closer to replicating this process, but they have not yet succeeded in producing mature sperm. The experimental cells were unable to fertilise an egg and were not used to create embryos.

For the time being, this is not a treatment for infertility, but a research model. It can be used to study the early development of male germ cells, investigate the causes of certain forms of infertility and, in the future, test the safety of new approaches.

Details

The experiment was based on induced pluripotent stem cells, or iPS cells. These are derived from ordinary adult cells by reprogramming them to a state from which they can once again develop into various types of tissue. In this study, human iPS cells were generated from blood cells. Separate experiments were carried out using cells from rhesus macaques.

Using a sequence of chemical signals, the researchers guided the iPS cells along the path towards the formation of germ cells. Initially, cells similar to the embryo’s primordial germ cells appeared. Under natural conditions, it is from these that egg cells or sperm subsequently develop.

Chemical signals alone proved insufficient. For further development, the future germ cells require a complex environment comprising surrounding tissues, hormones and signalling molecules.

To create such an environment, the scientists mixed human or monkey cells with supporting cells derived from the testes of mouse embryos. The mixture spontaneously organised itself into a three-dimensional structure, which the authors termed a ‘xenogeneic reconstructed testis’. Put simply, this is a model of testicular tissue assembled from cells of different species.

Structures resembling seminiferous tubules began to form within it. These are the thin tubes in which sperm develop in a real testis.

However, the structure did not grow solely in laboratory dishes. It was transplanted beneath the capsule of the kidney in immunodeficient mice. This location is well supplied with blood, so the cells were able to receive oxygen and nutrients and develop over the course of several months.

As a result, the human cells reached the spermatogonial stage – the early precursors of sperm cells. The researchers also found a small number of cells that were just beginning to prepare for meiosis. This is the name given to the specialised division during which a future sex cell receives half a set of chromosomes.

In terms of appearance, protein composition and gene activity, the cultured cells resembled natural human and macaque germ cells at the corresponding stage of development. However, they did not complete meiosis and did not develop into mature spermatozoa with tails.

The researchers also discovered that the proteins NANOS3 and DND1 help early germ cells to survive and prevent them from developing into cells of other tissues. Retinoic acid — a derivative of vitamin A — played a role in triggering their further maturation. This laboratory observation does not mean that taking vitamins can influence infertility or replace medical treatment.

Why this is important

Some forms of male infertility are linked to the process of germ cell formation stalling at one of the early stages. Studying such disorders is challenging: sperm development takes a long time and depends on the precise interaction of several types of cells within the testis.

Experiments on mice provide a great deal of useful information, but the development of germ cells in rodents and primates differs significantly. Therefore, results obtained from mice cannot automatically be extrapolated to humans.

The new model allows researchers to observe how human and monkey cells progress through the early stages of development. In future, scientists will be able to switch off individual genes, alter the culture conditions and determine at which stage and for what reason the process is disrupted.

In theory, such technologies may one day help people whose bodies do not produce their own sperm. For example, a patient’s ordinary cells could be reprogrammed and guided along the path to germ cell formation. However, to achieve this, researchers must first learn how to produce fully functional sperm, verify their genetic and epigenetic safety, and resolve serious ethical and legal issues.

Background

Sperm formation is a multi-stage process. Spermatogonia divide, then develop into spermatocytes, undergo meiosis, and only then become sperm. An error at any stage can lead to infertility or genetic abnormalities.

Scientists have already managed to complete this entire process in experiments using mouse cells. In humans and other primates, the process usually stops much earlier — before meiosis is complete.

The main problem is that germ cells do not develop on their own. They require a specific cellular environment, which is difficult to replicate in laboratory conditions. The authors of the new study have partially solved this problem by combining primate stem cells with mouse supporting cells and implanting the construct into an animal’s body.

This makes the experiment an important intermediate step. It demonstrates that the development of human germ cells can be taken further, but at the same time highlights just how challenging it remains to produce mature sperm entirely in the laboratory.

Source

The study by Eoin Whelan, Minyue Guo, Kotaro Sasaki and their colleagues, ‘Generation of spermatogonia from human and non-human primate pluripotent stem cells’, was published in the journal *Cell Stem Cell* in 2026.