Researchers have cracked the code for male fertility

Every cell contains a set of instructions in its DNA that determine which genes will be expressed and which will be silenced. Correct programming of so-called epigenetic programs, including DNA methylation, is essential for fertilization and development.

A team of researchers from the University of Münster has for the first time identified the DNA methylation program underlying the process of sperm production (spermatogenesis) in humans. They discovered that during spermatogenesis, reprogramming of the entire genome occurs. What's more, when they analyzed cells from infertile men, they found that certain regions of the genome were misprogrammed, revealing a new potential cause of male infertility.

The code has been cracked, at least the one that leads to sperm production in humans. To successfully complete this process, the genes involved in it need “instructions.” In other words, in order for the germline to generate sperm through the process of spermatogenesis, certain chemical patterns must be established in the DNA.

A research team led by Dr. Sandra Laurentino and Professor Nina Neuhaus from the Center for Reproductive Medicine and Andrology (CeRA) at the Faculty of Medicine of the University of Münster has now discovered the specific instructions behind this. Moreover, the Münster researchers also identified a new possible cause of male infertility based on genomic misregulation. These results were published in the American Journal of Human Genetics.

The translational research, led by biochemist Laurentino and biologist Neuhaus, focused on DNA methylation, a type of chemical modification in DNA that regulates genes. This forms a kind of computer program in which the genes of various cells are "turned on and off" to allow spermatogenesis to progress.

The testicle, where sperm production occurs, is a very complex tissue, explains Dr. Laurentino. This is why the “instructions” behind spermatogenesis remained unknown until now.

The research team achieved a breakthrough with colleagues from the Max Planck Institute for Molecular Biomedicine in Münster, now at Imperial College London, when they found a way to separate sperm-producing cells from the rest of the testicular tissue.

Using sophisticated sequencing techniques, the team was able to crack the fertility code - a milestone in epigenetics, the discipline that deals with potentially heritable modifications that regulate gene activity.

A surprising and intriguing result of the study was the research team's discovery that the code does not function correctly in men suffering from extremely low sperm production, technically called cryptozoospermia. This has uncovered a previously unknown cause of male infertility and implies new therapeutic approaches that require further research.