Mosaicism for 45,X cell line may accentuate the severity of spermatogenic defects in men with AZFc deletion

Editor—Over the past 10 years, several authors have reported microdeletions in the long arm of the Y chromosome (Yq) in men with idiopathic, non-obstructive azoospermia or severe oligospermia. These microdeletions were clustered on the Yq fragment previously described as the azoospermia factor region (AZF).1 More recently, a number of genes expressed specifically in the testes and mapping to AZFa, AZFb, or AZFc subregions have been cloned.2-4 One of the approaches to understanding the role of these genes in human spermatogenesis is to look for a correlation between the lack of given AZF genes and the particular spermatogenic defect in the phenotypes of the patients. However, attempts to find such a correlation have failed so far. Instead, a broad spectrum of phenotypes ranging clinically from azoospermia to severe oligospermia and histologically from Sertoli cell only syndrome (SCOS) to hypospermatogenesis has been described in association with AZFc deletions.5 6 A recent study found chromosomal aberrations in 15% of azoospermic patients.7 However, in papers focusing on the analysis of AZF microdeletions in patients with idiopathic infertility,2 3 5 8-30 systematic, bilateral, histological, molecular, and cytogenetic analyses in the same large group of patients was rarely carried out, thus limiting information on the coexistence of AZF deletions and chromosomal aberrations. In this study, we propose and test the hypothesis that chromosomal defects may often accompany AZF deletions and cause the lack of a genotype-phenotype correlation in human male idiopathic infertility. We also attempt to evaluate the nature of the spermatogenetic failure associated with isolated AZFc deletions. For this purpose, we performed a dual genetic analysis of karyotypes and molecular status of the AZF region along with bilateral testicular histological evaluation in 94 patients with non-obstructive, idiopathic infertility and azoospermia, severe oligospermia, or oligospermia. Sixty five men with …

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