SUBMICROSCOPIC DELETIONS IN THE Y-CHROMOSOME OF INFERTILE MEN

Recent investigations have suggested a high prevalence of Y chromosome submicroscopic deletions in men with severely impaired spermatogenesi s, We evaluated the frequency of Y chromosome deletions in 160 inferti le men using a series of 36 sequence-tagged-sites, emphasizing interva ls 5 and 6 of the long arm of the Y chromosome, peripheral leukocyte D NA was extracted and amplified with two parallel techniques to minimiz e potential overestimation of the frequency of deletions, The presence of deletions was evaluated relative to patient's sperm concentration, testis volume, and hormonal parameters, Men with sperm concentration <5 x 10(6)/ml had a 7% prevalence of submicroscopic Y chromosome delet ions, Deletions were detected in 7% of azoospermic men, 10% of men wit h <1 x 10(6) spermatozoa/ml, and 8% of men with >1 x 10(6) but <5 x 10 (6) spermatozoa/ml. Other clinical parameters did not identify men wit h Y chromosome deletions prior to polymerase chain reaction (PCR)-base d testing for the presence of sequence-tagged-sites. Two distinct regi ons of Y chromosome deletions were detected, similar to 3.6 Mh and 1.4 Mb in length respectively, These deleted regions are present in AZFb and AZFc respectively, No deletions were detected in AZFa. The loss of these two distinct areas is supported by the finding of highly repeti tive sequences along the Y chromosome, predisposing to deletion of spe cific intervals on the Y chromosome during meiosis, Men with severe ma le infertility are at high risk for Y chromosome deletions, Testing of men for these genetic abnormalities is indicated prior to treatment w ith assisted reproduction.