Researchers set out to investigate possible genetic causes of otherwise unexplained male fertility problems by examining the NR5A1 gene, known to be involved in sexual development, in a group of men with unexplained low sperm counts seeking fertility treatment.
Of 315 men, seven were found to have mutations in NR5A1, whereas none of the control men (370 with at least two children and a further 359 with normal sperm counts) had any changes in the gene.
Four of the men with NR5A1 mutations had altered levels of sex hormones and one had a minor structural abnormality of the testes. Functional studies showed that the mutations caused altered function of the NR5A1 protein, which regulates the expression of other genes.
The authors concluded that mutations in the NR5A1 gene account for approximately 4% of cases of unexplained male fertility, and propose that careful clinical investigation is necessary for men who do not produce sperm normally.
Comment: This is a useful contribution to the currently very limited knowledge about genetic factors underlying male fertility, although the authors' conclusion that 4% of all cases are caused by mutations in this specific gene seems rather sweeping, despite the absence of any mutations in the control population, given the relatively small sample size and the limited data available for comparison.
A similar study of women with fertility problems would be of interest, since the same gene is reportedly involved in female sexual development.
Sources: Bashamboo A et al. Am J Hum Genet. DOI: 10.1016/j.ajhg.2010.09.009, BBC news