UCSF researchers have discovered a human gene that can be traced back through the mouse to the fly, illuminating a molecular nugget from ancient times that may play a crucial role in male fertility - and infertility.
The researchers suspect that the gene, known as BOULE, participates in the creation of sperm at a stage of development known as meiosis (which occurs only in the development of sperm and egg). When the like gene is deleted in the fly, a process similar to meiotic function is disrupted, preventing sperm development, and thereby causing male infertility.
"We think that the identification of genes like BOULE that are required for meiotic function is going to be very important clinically, because some 30 percent of infertile men have meiotic arrest during sperm development, and this is very similar to what you see in flies that have mutations in this gene," says the lead author of the study, Eugene Yujun Xu, PhD, a postdoctoral fellow in the laboratory of senior author Renee A. Reijo Pera, PhD, a leading researcher on sperm-related infertility in men and a UCSF assistant professor of obstetrics-gynecology and reproductive sciences.
The researchers are now examining whether deletions in the equivalent gene in mice cause meiotic arrest in the animals' developing sperm. They also are investigating whether the BOULE gene is altered in infertile men whose sperm have various developmental defects, particularly those with indications of meiotic arrest in the testes.
If a defect in BOULE does prove to be a cause of male infertility, it might be possible, says Xu, to treat the condition by introducing a normal copy of the gene into the testes through a nontoxic vector, where it could then replicate. The testis, unlike brain or heart, is located outside the main human body, limiting the possibility that the gene therapy approach would damage other tissues of the body, he says.