It is thought that around 15 percent of couples are infertile, and that many of these suffer from gametogenesis failure, meaning an inability to produce viable sex cells. Creating these in the lab has therefore emerged as a major goal for infertility treatment research, and has finally been achieved by a team of scientists in China, who have managed to grow fully functioning mouse sperm from stem cells.
Male germ cells – or sperm – are formed by a complex process called spermatogenesis, which begins with the specification of embryonic stem cells into primordial germ cells (PGCs) that then divide by meiosis. This differs from the process by which all other cells divide – known as mitosis – as it produces gametes, which contain only half of the number of chromosomes of the original cell.
Replicating meiosis outside of the body has remained a major obstacle for scientists, and while some previous studies have managed to partially achieve this, none had met the agreed-upon “gold standard” criteria for the full creation of in vitro gametes. To attain this, researchers must demonstrate the correct replication of every stage of meiosis, includingsynapsis and recombination, which refer to the division and re-joining of chromosomes. Additionally, the gametes produced must be capable of producing viable offspring.
Describing their work in the journal Cell Stem Cell, the researchers explain how they were able to stimulate the specification mouse embryonic stem cells into PGC-like cells by surrounding them with testicular tissue from mice that had been genetically engineered to produce high levels of testicular retinoic acid, which is known to initiate spermatogenesis. They then experimented with the addition of a number of sex hormones, including testosterone, follicle-stimulating hormone and bovine pituitary extract, noting that the presence of all three of these together promoted meiosis.
One of the pups born from the mouse sperm grown by the researchers. Zhou, Wang, and Yuan et al
Genetic analysis revealed the presence of a number of compounds that are known to be involved in chromosomal synapsis and recombination, indicating that all the relevant stages of meiosis had indeed occurred.
The gametes produced by this process were then used to fertilize mice eggs, which were implanted into female mice and developed into embryos, eventually giving rise to healthy pups. These pups all survived to adulthood and produced their own viable offspring, indicating that the process had been a success.
More research is needed in order to determine if this technique can be used for human reproduction, although the study authors are hopeful that their work provides a starting point for the development of novel treatments for male infertility.