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Each cell contains a set of instructions in their DNA that determines which genes are expressed and which are silenced. The correct programming of these so-called epigenetic programmes, including DNA methylation, is essential for fertilisation and development. A team of researchers from the University of Münster have for the first time identified the DNA methylation programme behind sperm production (spermatogenesis) in the human. They found that during spermatogenesis the entire genome is reprogrammed. Moreover, when they analysed cells from infertile men, they found that some regions in the genome are not correctly programmed, revealing a new potential cause of male infertility.
The code has been cracked, at least the one leading to the production of sperm in humans. For this to be successful, the genes involved in the process need an “instruction manual”. In other words, 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 Centre of Reproductive Medicine and Andrology (CeRA) of the University of Münster Medical Faculty has now discovered the specific instructions behind this. On top of that, the Münster researchers also identified a new possible cause of male infertility based on faulty genome regulation. These results have now been published in the renowned American Journal of Human Genetics.
The translational study, led by biochemist Laurentino and biologist Neuhaus, focused on DNA methylation, a type of chemical modification in the DNA that regulates genes. This forms a sort of computer programme in which genes of different cells are “switched on and off” in order for spermatogenesis to progress. The testicle, where sperm is produced, is a very complex tissue, explains Dr Laurentino. This is why the “instructions” behind spermatogenesis remained unknown until now. The research group achieved a breakthrough with colleagues from the Max Planck Institute for Molecular Biomedicine in Münster, who are now working at Imperial College London, when they found a way to separate the cells that produce sperm from the remaining testicular tissue. Using a sophisticated sequencing technique, the group was able to decipher the fertility code - a milestone in epigenetics, the discipline that deals with potentially inheritable modifications regulating the activity of genes.
A surprising and intriguing outcome of the study occurred when the research team found that the code does not function correctly in men who suffer from extremely low sperm production, technically termed cryptozoospermia. This revealed a previously unknown cause of male infertility and suggests new therapeutic approaches that require further research.
Dr Sandra Laurentino
University of Münster | University Hospital Münster
Centre of Reproductive Medicine and Andrology
E-Mail: Sandra.Laurentino@ukmuenster.de
Siebert-Kuss LM, Dietrich V, Di Persio S, Bhaskaran J, Stehling M, Cremers JF, Sandmann S, Varghese J, Kliesch S, Schlatt S, Vaquerizas JM, Neuhaus N, Laurentino S. Genome-wide DNA methylation changes in human spermatogenesis. Am J Hum Genet. 2024 Jun 6;111(6):1125-1139. https://doi.org/10.1016/j.ajhg.2024.04.017
https://www.medizin.uni-muenster.de/en/cera.html Centre of Reproductive Medicine and Andrology
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