Expression of BET genes in testis of men with different spermatogenic impairments

Objective: To characterize the BET gene expression in human testis with spermatogenetic impairments; to examine BRDT protein expression in testis and semen. Design: Prospective study. Setting: Fertility clinic. Patient(s): Azoospermic men (n = 120) who underwent testicular sperm extraction and who were classified as either normal spermatogenesis, mixed atrophy, spermatocyte maturation arrest, or Sertoli cells only according to their combined histologic and cytologic testicular findings and three normozoospermic men who donated sperm. Intervention(s): Evaluation of testicular biopsies by qualitative and quantitative reverse transcriptase-polymerase chain reaction, immunohistochemical staining, and analysis of spermatozoa by immunofluorescence. Main Outcome Measure(s): Expression of the four BET genes in testis and localization of BRDT protein in testicular tissue and ejaculated spermatozoa. Result(s): The BRDT gene was not expressed in testicular tissue from patients with Sertoli cells only, whereas the other three genes of the BET family retained expression in all the pathologies. The BRDT protein was localized in the nuclei of spermatocytes, spermatids, and ejaculated spermatozoa. Expression of BRDT protein was almost nil in testicular tissue specimens with spermatocyte maturation arrest despite normal transcript levels. Conclusion(s): Human BRDT expression pattern differs from mouse BRDT expression. In human, BRDT is the only BET gene expressed exclusively in testicular germ cells. Its expression in elongated spermatids and ejaculated spermatozoa raises the possibility that it is involved in unidentified additional functions.