Researchers at the University of Pennsylvania explored how the DOT1L enzyme supports the ongoing production of sperm in adult mice. The findings, published in Genes and Development, illuminate a key mechanism that enables male fertility to persist over time by maintaining the health of the cells that birth sperm.
In mammals, the continuous creation of sperm depends on the persistent renewal of a specialized group of stem cells within the testes. The studies show that DOT1L acts as a crucial self renewal factor for these germline stem cells. When DOT1L is absent, this renewal process falters, and the ability of the testes to sustain sperm production diminishes, ultimately impacting fertility in the organism.
The researchers arrived at their conclusions somewhat by chance. When DOT1L was disrupted across all cells in embryos, the animals did not survive to birth, prompting an experiment focused on changing the gene specifically in testicular stem cells. In other animals where the mutation was not inherited, sterility followed. Moreover, altering the DOT1L gene in adult mice produced a similar loss of stem cell renewal. The authors propose that DOT1L may modulate the activity of the Hoxc gene family, a set of transcription factors that control the expression of multiple genes during development and cell differentiation.
Prior investigations by other groups had studied DOT1L mainly in the context of leukemia. When DOT1L is overexpressed in progenitor cells of the blood, it can contribute to malignant growth. This line of research holds promise for deepening the understanding of leukemia and could point toward future avenues for reprogramming body cells into germ cells, potentially advancing infertility treatments in time.