Y chromosome haplogroups: A correlation with testicular dysgenesis syndrome?

Abstract

Testicular dysgenesis syndrome encompasses low sperm quality, hypospadias, cryptorchidism and testicular cancer. Epidemiological studies and genetic data from familial cases suggest that testicular dysgenesis syndrome has a common etiology. The Y chromosome is known to encode genes that are involved in germ cell development or maintenance. We have therefore investigated if different classes of Y chromosomes in the general population (Y chromosome haplogroups) are associated with aspects of the testicular dysgenesis syndrome. We defined the Y chromosome haplogroups in individuals from different European counties who presented with either (i) oligo- or azoospermia associated with a Y chromosome microdeletion, (ii) unexplained reduced sperm counts (<20 x 10(6)/ml) or (iii) testicular cancer. We failed to find Y chromosome haplotype associations with either microdeletion formation or testicular cancer. However, in a study of the Danish population, we found that a specific Y chromosome haplogroup (hg26) is significantly overrepresented in men with unexplained reduced sperm counts compared with a Danish control population. The factors encoded by genes on this class of Y chromosome may be particularly susceptible to environmental influences that cause testicular dysgenesis syndrome. Our current data highlight the need for further analyses of clinically well-defined patient groups from a wide range of ethnic and geographic origins.