Researchers identify piRNAs as a highly relevant genetic cause of male infertility
Many couples struggle with infertility. Contrary to popular belief, men are just as often the cause of an unfulfilled desire for children as women – and genetics play a significant role in this. Researchers from the Institute of Reproductive Genetics at the University of Münster have now provided ground-breaking new insights on this topic. The study, published in "Nature Communications," shows for the first time that disruptions in the so-called piRNA pathway are an underestimated cause of defective sperm production.
Many couples struggle with infertility. The common belief that the cause typically lies with the woman is both widespread and mistaken. It is now clear that male factors are equally likely to contribute to couple infertility - and genetics play a significant role in this. The research teams led by Dr Birgit Stallmeyer and Prof Frank Tüttelmann from the Institute of Reproductive Genetics at the University of Münster have now provided ground-breaking new insights: Their study, published in the renowned journal Nature Communications, is the first to show that disruptions in the so-called piRNA pathway are an underestimated cause of defective sperm production.
RNA, short for ribonucleic acid, is a single-stranded molecule composed of nucleotides present in every cell of an organism and acts as a carrier of genetic information. PiRNA refers to specialised, very small RNA fragments found in the testes that help suppress the activity of transposons, also known as jumping genes. “The piRNA pathway has largely been studied in mice, with limited data on humans”, says Stallmeyer. To address this, the researchers analysed the DNA of over 2,000 infertile men, mostly from the Münster Centre for Reproductive Medicine and Andrology, for variations in piRNA pathway genes. “We identified 39 men with variations in 14 piRNA genes, many of which are reported here for the first time. Our findings reveal that faulty regulation of piRNAs is a far more common cause of male infertility than previously recognised”, she explains. The impact of these genetic variants on sperm production differed between humans and mouse models, suggesting that findings from mice are not universally applicable to humans.
In some patients with piRNA variants, an increased number of transposons was detected. “A higher count of jumping genes in germ cells causes genomic instability, leading to various disruptions in sperm production, from abnormal shapes to complete absence of sperm”, says Prof. Frank Tüttelmann, Director of the Institute of Reproductive Genetics and the Centre of Medical Genetics and last author of the study.
While the newly discovered disruptions in the piRNA pathway cannot yet be treated, these insights will help provide more men with an accurate diagnosis in the future – offering relief to many who have faced years of uncertainty. “Further research will help us identify which patients can successfully have sperm retrieved through a testicular biopsy and sperm extraction for medically assisted reproduction. Conversely, we aim to determine who would not benefit from this procedure, allowing for more targeted treatments”, says Tüttelmann. The study was funded by the Interdisciplinary Centre for Clinical Research (IZKF) of the Medical Faculty and was conducted in international collaboration with researchers from the University of Edinburgh, the University of Newcastle, and Oregon Health & Science University in the USA.
Wissenschaftlicher Ansprechpartner:
Prof. Dr. Frank Tüttelmann
Institute of Reproductive Genetics (IRG)
University of Münster
Tel.: +49 (251) 83-55411
E-Mail: Frank.Tuettelmann@ukmuenster.de
Dr. Birgit Stallmeyer
Institute of Reproductive Genetics (IRG)
University of Münster
Tel.: +49 (251) 83 – 53234
E-Mail: Birgit.stallmeyer@ukmuenster.de
Originalpublikation:
Stallmeyer B, et al. Inherited defects of piRNA biogenesis cause transposon de-repression, impaired spermatogenesis, and human male infertility. Nat Commun. 2024 Aug 9;15(1):6637. doi: https://doi.org/10.1038/s41467-024-50930-9
Weitere Informationen:
https://www.medizin.uni-muenster.de/en/reprogenetik/the-institute.html Institute of Reproductive Genetics (IRG)
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