Professor Rob McLachlan, the Hudson Institute author and is one of a number of international researchers who have published this study.
A genetic basis for male infertility is an active area of research worldwide. Many genes have been proposed based on animal models but few have proven relevant to the human. It is important that candidate mutations be rigorously assessed before they earn a place in the clinical evaluation. Recently the list of causative mutations in male infertility has been increasing rapidly.
The piwi-like RNA-mediated gene silencing 1 (PIWIL1; also known as HIWI) gene is involved in spermatid chromosome modelling, and a mutation in its D box area has been linked to azoospermia in animals and the human by Gou et al [Cell Research; 2017].
This current paper sought to establish whether this gene is indeed relevant to human male infertility, and represents a major international collaborative effort run from the Dept of Human Genetics at Radboud University in the Netherlands, along with numerous other European, UK and American centres, and Monash University/Hudson Institute.
The Monash Male Infertility DNA database, developed over the past 25 years, was utilised to contribute many clinical samples to the overall study of 1950 azoospermic and 790 severely oligospermic men. No PIWIL1 D box mutations were found as proposed by the previous authors. The study investigators went on to explore potential variants elsewhere in the gene and, while some minor variants were found, these were at no greater rate as compared to 3347 controls. There were several heterozygous loss of function variants seen, including in control men, and it was considered unlikely that they would likely cause disease in the haploinsufficient state.
This is an important negative study which has excluded mutations in the D box region of the PIWIL1 gene as a cause of human azoospermia. Such vigilance is important in developing clinical testing panels.
Centre for Endocrinology and Metabolism
Journal and article title
The results were not surprising as such. There have been many candidate genes for causes of infertility, some of which have been eliminated as contenders on closer investigation, like this one. The findings are not novel but are important, as indicated by their publication in such a high impact journal.
Infertility can be most distressing for many people who are unable to have children, particularly when the cause is not known. The more information that is known about the causes of infertility, the more hope there will be for treatments to be developed to assist people who are unable to conceive children. This study provides information about one gene that had been proposed as a cause of male infertility. The quality of life of people experiencing infertility will be improved by studies such as this which allow focus to be directed to the genes that may be causative of the condition.
Human male infertility
Other points of interest
The study is a major international collaborative effort run from the Department of Human Genetics at Radboud University in the Netherlands, along with numerous other European, UK and American centres, and Monash University/Hudson Institute.
Professor Rob McLachlan’s involvement in this study is clinical sample acquisition over many decades as well as clinical input. The driving force for the Australian contingent of this international collaboration is Professor Moira O’Bryan, formerly of MIMR and Monash University, and currently of the University of Melbourne.