Expression of the apoptosis inhibitor survivin in testicular tissue of infertile patients

Abstract

Summary Apoptosis is a common phenomenon during spermatogenesis, and its dysregulation has been associated with male infertility. Survivin is an inhibitor of apoptosis protein that regulates apoptosis at cell division and is overexpressed in common human cancers. We investigated whether survivin mRNA expression is detectable in testicular biopsies from patients with infertility of varying aetiology. The aim of this study was to examine the testicular survivin expression in azoospermic men with normal spermatogenesis and in those with specific spermatogenic disorders. Survivin mRNA expression was detected by reverse transcriptase-polymerase chain reaction in histologically classified testicular biopsy specimens from 30 azoospermic men. Survivin was found to be expressed in normal spermatogenesis (n = 10), in post-meiotic spermatogenic arrest (n = 6), and in specimens showing a mixed picture of pre-meiotic maturation arrest with sparse islands of post-meiotic arrest (n = 2). In contrast, a lack of survivin expression was seen in specimens without haploid germ cells (pre-meiotic maturation arrest, n = 2) and in those with Sertoli-cell-only syndrome (SCOS, n = 10). These data indicate for the first time that survivin is expressed in human testis. Moreover, its expression seems to correlate with the stage of maturation arrest in patients presenting with spermatogenic disorders. Survivin mRNA expression was not found in SCOS specimens, possibly indicating germ-cell-specific expression in human testicular tissue. Thus, survivin is a potential molecular marker of spermatogenesis, whose expression is altered in specific spermatogenic disorders.

Status of the executioner step of apoptosis in human with normal spermatogenesis and azoospermia

“…Although apoptosis has been identified in men with different types of spermatogenetic failures (10,11,(18)(19)(20)(21), the profile of the executioner step of apoptosis has not been determined in testicular tissue with normal or abnormal histology. However, in the human testes, procaspase-3 has been detected in germ and Sertoli cells (21), whereas by analyzing testicular tissue with spermatogenetic failures the survivin mRNA was detected in germ cells (22,23). Localization of the other caspases, IAPs such as XIAP, and the IAP inhibitor Smac/ DIABLO has not been yet reported in human testes.…”

Survivin Downregulation Is Associated with Vasectomy-Induced Spermatogenic Damage and Apoptosis

“…Survivin gene expression was found to be altered in certain spermatogenic disorders. The studies of Weikert et al [5] have shown that testicular survivin levels in infertile patients were related inversely to the severity of spermatogenic failure (p ! 0.001), with a lack of expression in most specimens with premeiotic spermatogenic arrest and in all those with germ cell aplasia [10,11] .…”

“…Its role in regulating cellular proliferation, cell cycle and programmed cell death made it a good candidate gene for regulating germ cell apoptosis [4] . One of the early indications of its possible role in human spermatogenesis came from a study by Weikert et al [5] . The group demonstrated that survivin is downregulated in spermato-genic disorders, which implicated it as a regulatory factor in germ cell proliferation and apoptosis with a possible role in human spermatogenesis.…”

Contribution of environmental pollutants to male infertily: A working model of germ cell apoptosis induced by plasticizers

“…Germ cell apoptosis has been shown to play an important role in controlling sperm output in many species and has been linked to infertility in humans (Feng et al, 1999;Weikert et al, 2004;Ji et al, 2009). Germ cells undergoing meiosis (spermatocytes) are highly sensitive to heat shock, ionizing radiation, growth factor deprivation, and chemotherapeutic agents (Russell, 2004;Bieber et al, 2006;Lizama et al, 2009;Silva et al, 2011).…”