Possible Cause of Male Infertility Discovered

Researchers at the University of North Carolina at Chapel Hill under the lead of Yi Zhang, a Howard Hughes Medical Institute (HHMI) investigator, in collaboration with researchers of the Laboratory of Reproductive and Developmental Toxicology at the National Institute of Health, discovered a possible link between the protein Jhdm2a and fertilization. Thus far, the research has only been limited to observations in mice. However, because there are similarities in regard to the function of the protein in mice and humans, the researchers believe the protein or the lack thereof also plays a role in the human fertilization process.

In order for the sperm to enter the egg it needs to tighten itself up into a small ball first. This allows the sperm to penetrate the thick and tight outer layer of the egg. According to the scientists, the protein they have discovered has an affect on the way the DNA inside the sperm is stored allowing for maximum tightness when the sperm scrunches up. Studies on mice have shown the sperms' inability to penetrate the egg if the protein is missing, because the genetic material cannot be stored tightly within the sperm.

The enzyme studied by the scientists is the Jhdm2a protein. As a histone demethylase enzyme, it sets off gene activity. According to earlier research performed by the team, the gene's activity for this particular protein is very high in the testis with the highest protein levels occurring during sperm maturation. In tests performed in mice, the Jhdm2a gene was removed, which caused deficient sperm development. Further examination revealed the DNA inside the sperm did not properly condense as needed for the fertilization process.

The researchers determined, in order for this condensation process to take place the Jhdm2a histone protein has to activate the genes for two other proteins, transition nuclear protein 1 (Tnp1) and protamine 1 (Prm1). Without Jhdm2a present, these to basic proteins cannot be activated. Fertilization cannot take place.

Because there are similarities in the role demethylase proteins have in gene regulation for mice as well as humans, the researchers believe the lack of Jhdm2a activity in a human male could be one of the causes of male infertility. Therefore, drugs that would stimulate or simulate Jhdm2a activity could be of benefit in the treatment of male infertility. Similarly, a drug that stops Jhdm2a activity could be useful as a male birth control measure.