A recent study published in eLife reveals that men with an unstable Y chromosome subtype are at a significantly higher risk of fertility problems. These men are up to nine times more likely to face issues related to sperm production (spermatogenesis), often due to genomic rearrangements in their DNA. The findings suggest that molecular diagnostics could help identify individuals at risk early, providing them with the opportunity to make informed decisions about family planning. Currently, the cause of infertility remains unclear for more than half of men with spermatogenic impairment.
The large-scale study, led by geneticist Pille Hallast, analyzed the Y chromosomes of over 2,300 men from Estonia. The research was a collaboration between the Human Genetics Research Group at the University of Tartu, the Andrology Centre of Tartu University Hospital, and the Wellcome Sanger Institute. The men in the study were recruited through the Andrology Centre, led by Professor Margus Punab.
This Y-chromosomal region has previously been linked to male infertility, but this is the first time it has been studied in such a large clinical sample. Hallast described the study as the most in-depth analysis of the Y chromosome variation in men with spermatogenic issues.
Professor Maris Laan, a senior co-author and Professor of Human Genetics at the University of Tartu, explained that the study uncovered a previously unknown subtype of Y chromosome. This subtype is linked to a high risk of severe spermatogenic impairment. The instability of this Y chromosome is caused by the inversion of a DNA segment during evolution, which leads to deletions in surrounding regions of the chromosome. These genetic deletions can cause infertility but do not always lead to issues, making it possible for the variant to go unnoticed in families until fertility problems arise.
The inverted Y chromosome variant is relatively common, especially among men of European descent, though it is not as widespread in other parts of the world. In Estonia, about 5-6% of men carry this subtype, while the figure rises to nearly 20% in Poland and the Czech Republic. However, only about one in ten men with this variant experience the genetic deletions that impact sperm production.
Dr. Chris Tyler-Smith, a leading population geneticist at the Wellcome Sanger Institute, emphasized the importance of collaborative research to identify harmful Y-chromosomal variants. He noted that understanding how these variants have evolved and persisted could offer valuable insights into infertility and help guide future clinical research.
Professor Laan highlighted the potential benefits of molecular diagnostics, as identifying the genetic cause of spermatogenic impairment early could lead to more focused treatment for infertile couples. With this new understanding of the Y chromosome, doctors can better manage infertility cases based on the specific genetic makeup of the individuals involved.
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