Y-chromosome microdeletion and phenotype in cytogenetically normal men with idiopathic azoospermia.
OBJECTIVE
To determine the prevalence of microdeletions of the long arm of chromosome Y within the AZFa, AZFb, and AZFc subregions in patients with idiopathic azoospermia, and then correlate the microdeletions with clinical phenotypes to determine the most important subregion for screening.


METHODS
Controlled clinical study.


METHODS
Male infertility clinic, Kobe University Hospital.


METHODS
Among 89 consecutive azoospermic patients, those whose infertility was related to known hereditary, endocrine, or obstructive causes or a cytogenetic abnormality were excluded; 54 remaining patients were studied using a polymerase chain reaction (PCR). Of these patients, 33 had Sertoli cell only syndrome, 10 had maturation arrest, and 11 had hypospermatogenesis.


METHODS
Blood and semen samples and testicular biopsies were obtained from all of the participants.


METHODS
We performed semen analysis, polymerase chain amplification of 28 DNA loci on the long arm of the Y chromosome involving the DAZ (deleted in azoospermia), and measured the plasma FSH, LH, testosterone, prolactin, and estradiol levels.


RESULTS
Microdeletions were detected in 14 of the 54 patients (nine with Sertoli cell only, three with maturation arrest, and two with hypospermatogenesis). Most microdeletions involved AZFb or AZFc. Patients with hypospermatogenesis or maturation arrest showed deletion only in AZFc. The DAZ gene was deleted in four patients with Sertoli cell only and one patient with maturation arrest. The RBM gene was deleted in two patients with Sertoli cell only who had particularly large deletions, but in no patients with arrest or hypospermatogenesis.


CONCLUSIONS
Cytogenetically azoospermic patients should be examined for microdeletions before undertaking assisted reproduction. AZFc may be the most important subregion to screen. In addition, intact AZFa and AZFb subregions may be important for the presence of germ cells.
Fujisawa
M
M
Division of Urology, Department of Organ Therapeutics, Kobe University Graduate School of Medicine, Kobe, Japan. masato@med.kobe-u.ac.jp
Shirakawa
T
T
Kanzaki
M
M
Okada
H
H
Arakawa
S
S
Kamidono
S
S
D000328:Adult; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D004958:Estradiol / Q000097:blood; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D009845:Oligospermia / Q000097:blood / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D011388:Prolactin / Q000097:blood; D012016:Reference Values; D012661:Semen / Q000166:cytology; D012708:Sertoli Cells / Q000166:cytology / Q000473:pathology; D013091:Spermatogenesis; D013737:Testis / Q000033:anatomy & histology; D013739:Testosterone / Q000097:blood; D014998:Y Chromosome
D013739:Testosterone; D004958:Estradiol; D011388:Prolactin; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone