Simultaneous expression analysis of deleted in azoospermia-family genes and CDC25A: their potential as a predictor for successful testicular sperm extraction

Abstract

The Deleted in Azoospermia (DAZ) gene family consists of two autosomal genes, BOULE and DAZ-L (DAZ-like), and the DAZ gene cluster on chromosome Y. These genetic factors encode for RNA-binding proteins that are mainly expressed in germ cells and are considered essential for male fertility. Dysfunctions of these genetic factors lead to abnormal spermatogenesis and may cause male infertility that requires the use of testicular sperm extraction (TESE) for spermatozoa recovery. We analysed mRNA and protein expression of DAZ, DAZ-L, BOULE and the cell cycle regulator CDC25A, in testicular biopsies from patients with hypospermatogenesis and maturation arrest. DAZ gene family proteins were detected by immunohistochemistry in the germ cells in all biopsies. Individual expression level of DAZ, DAZ-L, BOULE and CDC25A showed no significant differences between hypospermatogenesis and maturation arrest biopsies. However, when all DAZ family members were simultaneously analyzed, we detected positive correlations between the expression level of DAZ/DAZ-L, DAZ/BOULE, DAZ-L/BOULE, DAZ-L/CDC25A and CDC25A/BOULE (p<0.05). Moreover, a significant increase in the expression of BOULE and CDC25A was detected in biopsies with successful sperm retrieval vs. biopsies with failed sperm retrieval (p<0.05). These results show that the simultaneous analysis of DAZ gene family members and CDC25A correlates with the spermatogenic damage in patients with hypospermatogenesis and maturation arrest and arises as a potential molecular predictor of sperm retrieval success by TESE.