Researchers have found that targeted delivery of messenger RNA (mRNA) can restore sperm production and fertility in genetically infertile male mice. The findings , published today in Stem Cell Reports, demonstrate that transient mRNA treatment restored sperm production and enabled the birth of healthy offspring.
Up to 10% of couples worldwide are affected by infertility, according to World Health Organization estimates, and male factors are the primary cause in about half of those cases. In many instances, male infertility results from genetic defects that disrupt sperm production.
To develop a targeted method to address genetic defects linked to infertility, Takashi Shinohara of Kyoto University, Japan, and his team injected mRNA – a short-lived molecule containing the blueprint of a gene of interest – into the testes of mice. The use of mRNA was specifically chosen to avoid permanent genetic modification of testis cells or other cells in the body.
The researchers first confirmed that this approach successfully delivered the genetic blueprint to the relevant cell types – sperm-producing cells and supporting Sertoli cells in the testis. They then tested whether mRNA delivery could restore fertility in male mice carrying a specific genetic defect in Sertoli cells that blocks sperm production. This defect has also been implicated in human infertility and testicular disorders.
Delivery of mRNA, which remained active for two days, was sufficient to unblock spermatogenesis in these genetically infertile mice. Importantly, sperm collected from treated animals generated healthy pups when injected into mouse oocytes by in vitro fertilization.
This work demonstrates that mRNA delivery can rescue a specific genetic defect underlying male infertility in mice. Additional studies in animal models will be required to evaluate safety and efficacy before considering potential clinical applications in human patients.
About Stem Cell Reports
Stem Cell Reports is the open access, peer-reviewed journal of the International Society for Stem Cell Research (ISSCR) for communicating basic discoveries in stem cell research, in addition to translational and clinical studies. Stem Cell Reports focuses on original research with conceptual or practical advances that are of broad interest to stem cell biologists and clinicians. Stem Cell Reports is a Cell Press partner journal. Find the journal on X: @StemCellReports.
About ISSCR
Across more than 80 countries, the International Society for Stem Cell Research (@ISSCR) is the preeminent global, cross-disciplinary, science-based organization dedicated to advancing stem cell research and its translation to medicine.
