SEVERE OLIGOZOOSPERMIA RESULTING FROM DELETIONS OF AZOOSPERMIA FACTORGENE ON Y-CHROMOSOME

Background About 13% of cases of non-obstructive azoospermia are cause d by deletion of the azoospermia factor (AZF), a gene or gene complex normally located on the long arm of the Y chromosome. Oligozoospermia is far more common than azoospermia, but little is known about genetic causes. We investigated whether severe oligozoospermia is caused by A ZF deletions and, if so, whether those deletions are present in mature spermatozoa, Methods By PCR, we tested leucocyte DNA, from 35 men who presented at infertility clinics and who had severe oligozoospermia, for the presence of 118 DNA landmarks scattered across the Y chromosom e. In the two men in whom Y-chromosome deletions in leucocyte DNA were detected, we also tested leucocyte DNA from the individuals' fathers, and in one man we tested sperm DNA. Findings In two men with ejaculat e sperm counts of 40 000-100 000 per mL, we detected Y-chromosome leuc ocyte DNA similar in location to those reported in azoospermic individ uals. No Y-chromosome deletions were detected in the fathers of the tw o men, For one of the two men, sperm DNA was tested, and it showed the same Y-chromosome deletion seen in leucocytes. Interpretation The Y-c hromosome deletions in these two men are de-novo mutations, and are th erefore the cause of their severe oligozoospermia. Not only is the abs ence of AZF compatible with spermatogenesis, albeit at reduced rate, b ut also the resultant sperm bear the mutant Y chromosome. Because intr acytoplasmic sperm injection is increasingly used as a means of circum venting oligozoospermia, AZF deletions could be transmitted by this pr actice, and would probably result in infertile sons. In cases of sever e oligozoospermia, it may be appropriate to offer Y-DNA testing and ge netic counselling before starting assisted reproductive procedures.