Mutations and infertility
Researchers from Newcastle University have shown that mutations not inherited from the father or mother play an important role in male infertility. These mutations occur during DNA replication in the germ cells of the parents and manifest much later.
Professor Joris Veltman from the Institute of Biological Sciences at Newcastle University led the study, which involved patients from the Newcastle Fertility Center and Radboud University Medical Center in the Netherlands.
Most genetic studies are devoted to recessive inherited infertility, in which both parents are carriers of the mutation, and infertility occurs when the son receives both mutated copies. However, a new study has shown that de novo mutations that occur in parental germ cells during DNA replication play a big role in infertility of sons.
Scientists collected and studied the DNA of 185 infertile men and their parents. They identified 145 rare mutations that are likely to negatively affect male fertility.
29 of these mutations affect genes directly involved in spermatogenesis – the process of sperm development, as well as other cellular processes associated with it.
The team identified mutations in the RBM5 gene, which encodes a protein that is an important regulator of mRNA splicing of male germ cells. Previous studies in mice have also shown that this gene plays a role in male infertility. In a cohort of 2506 infertile patients, 6 rare pathogenic missense mutations affecting the RBM5 gene were found, while in a cohort of 5784 fertile men they were not.
It is important to note that these mutations mainly cause the dominant form of infertility, in which only one mutated gene is required. As a result, there is a 50 percent chance that infertility caused by these mutations will be transmitted to the male child (if assisted reproductive technologies are used), and this can lead to infertility in sons.
Millions of children have already been born using assisted reproductive methods, which means that some of these children may inherit infertility from their father.
It is known that up to 7% of men suffer from infertility and 50% of fertility problems in a heterosexual couple are associated with a man. In about half of the cases of male infertility, the cause remains unknown.
The authors will continue their research by examining the effects that these newly identified mutations have on spermatogenesis and overall fertility.
It is hoped that this new knowledge will help in the future to give more answers about the causes and the best treatment options available to infertile couples.
Article by M.S.Oud et al. A de novo paradigm for male infertility is published in the journal Nature Communications.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of Newcastle University: Breakthrough into the cause of male infertility.