Association of decreased expression of activator of CREM in testis (ACT) and incidence of spermatogenesis failure

Introduction: The program of gene expression during spermatogenesis is based on unique rules which govern post-meiotic transcription in male germ cells. One very special feature concerns the process of chromatin remodeling, that involves various unconventional steps expressed genes use alternative promoters and splice isoforms in male germ cells. cAMP response element modulator (CREM)-mediated gene expression is an essential regulatory mechanism for germ cell differentiation. CREM is a key transcription factor in differentiation of round spermatids into mature spermatozoa. It binds to CRE region in the promoters of target genes and regulates their transcription. During spermatogenesis, CREM is regulated by activator of CREM in testis (ACT), a tissue specific protein that activates CREM in a phosphorylation-independent fashion. ACT is a factor belonging to the class of LIM-only (LMO) proteins with a characteristic organization of four and a half LIM domain (FHL). ACT expression is testis specific and temporally coordinated with CREM during germ cell differentiation This study investigates the expression of ACT in testicular tissues of infertile men referred to ROYAN Institute.Materials and Methods: Local ethical approval was gained for this study and informed consent was given by patients. Testicular biopsies were collected from 12 infertile men referred to ROYAN Institute and underwent testicular sperm extraction (TESE). Through pathological and spermogram analyses, these samples distributed into 4 groups: obstructive azoospermia (positive control), severe oligoasthenoteratozoospermia, complete maturation arrest at spermatid level and sertoli cell only syndrome (negative control). The total mRNA was extracted from all samples and cDNA was amplified by RT-PCR. Then, quantitation of cDNA was performed using Real-Time PCR.Results: Results showed reduced expression of ACT in patients with severe oligoasthenoteratozoospermia, complete maturation arrest at spermatid level and sertoli cell only syndrome, in comparison to positive control (p≤0.05). Conclusions: According to our finding, it is concluded that reduced expression of ACT-coding gene can cause to disorder in post-meiotic transcription in male germ cells, leading to spermatogenesis failure.

Keywords:

Male infertility , Spermatogenesis , ACT , CREM