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Researchers have unraveled the code of male fertility
Last reviewed: 02.07.2025
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Each cell contains a set of instructions in its DNA that determine which genes will be expressed and which will be silenced. Proper 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 identified for the first time the DNA methylation program underlying the process of sperm production (spermatogenesis) in humans. They found that during spermatogenesis, the entire genome is reprogrammed. Moreover, when they analyzed cells from infertile men, they found that certain regions of the genome were incorrectly programmed, revealing a new potential cause of male infertility.
The code has been cracked, at least the one that leads to sperm production in humans. In order for this process to be successful, the genes involved need "instructions." In other words, in order for the germline to generate sperm through the process of spermatogenesis, certain chemical templates need to be installed 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 Medical Faculty of the University of Münster has now discovered the specific instructions behind this. What’s more, the Münster researchers have also identified a new possible cause of male infertility based on incorrect regulation of the genome. These findings 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. It forms a kind of computer program in which genes in different cells are "switched on and off" to ensure spermatogenesis progresses.
The testicle, where sperm production occurs, is a very complex tissue, explains Dr. Laurentino. That's why the "instructions" for spermatogenesis have remained unknown until now.
The research team achieved the 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 decipher the fertility code - a milestone in epigenetics, the discipline that deals with potentially heritable modifications that regulate gene activity.
A surprising and intriguing finding from the study was the team’s discovery that the code does not function correctly in men suffering from extremely low sperm production, technically called cryptozoospermia. This uncovers a previously unknown cause of male infertility and suggests new therapeutic approaches that require further research.