Scientists at the University of Pennsylvania discovered that mice need the DOT1L enzyme to continue producing sperm throughout their adult lives. The discovery was presented in the journal Genes and Development.
Men can continue to produce sperm throughout their adult life, but for this they need to constantly renew the special stem cells from which the sperm are born. As the scientists discovered, the stem cell self-renewal factor DOT1L plays an important role in this. They showed that animals lacking DOT1L are unable to consistently regenerate stem cells, which affects their ability to produce sperm.
The discovery was made almost by accident. Mice with a mutant form of DOT1L in all cells of the body died at the embryonic stage, so the scientists decided to investigate what would happen if the gene was changed only in testicular stem cells. Mice in which the mutation was not innate also became sterile. The same loss of stem cell renewal ability was observed when scientists made a change to the genome of an adult mouse. The study’s authors suggest that DOT1L apparently alters the activity of the Hoxc gene family, which are transcription factors that regulate the expression of other genes.
Previously, other scientific groups had studied DOT1L in the context of leukemia. Overexpression of the gene in progenitors of blood cells can lead to malignant neoplasms. Studying this important enzyme may allow scientists to better understand the nature of leukemia and reprogram body cells into germ cells, which will be a new frontier in infertility treatment in the future.