N-Acetyl-l-Cysteine Inhibits Apoptosis in Human Male Germ Cellsin Vitro¹

Abstract

Antioxidant defenses play a critical role in the regulation of programmed cell death, even when death is induced by nonoxidative stimuli. During spermatogenesis, most of the testicular germ cells degenerate by an apoptotic process that is under hormonal control. However, the exact mechanisms by which hormonal signals are transduced within the cells to direct their life, and whether other effectors of the apoptotic pathway, for example antioxidants, take part in the control of human germ cell survival, are not known. In the present study, testosterone and N-acetyl-L-cysteine (NAC), which is an antioxidant, an inhibitor of apoptosis in several systems, and a survival factor in human semen, were found to suppress programmed cell death in human testicular germ cells in vitro. The samples came from adult men undergoing orchidectomy for prostate cancer. Germ cell death was induced by incubating segments of seminiferous tubules under serum-free culture conditions. This apoptosis, detected by Southern blot analysis of DNA fragmentation, by DNA labeling in situ, and by morphological analysis under the electron microscope, was significantly inhibited by testosterone at concentrations of 10(-6) and 10(-7) mol/L. NAC concentrations of 125, 100, 50, and 25 mmol/L suppressed germ cell death in a dose-dependent manner. This inhibition was effective during 4, 24, and 48 h of incubation. Apoptotic cells were identified mainly as spermatocytes and early spermatids. Programmed cell death was also demonstrated in late spermatids. We conclude that NAC, which is an antioxidant, plays an important role in germ cell survival in the human seminiferous tubules in vitro. We also suggest NAC as a possible new therapeutic factor for some men with idiopathic oligospermia.

Protective action of N-acetylcysteine on sperm quality in cyclophosphamide-induced testicular toxicity in male Wistar rats

“…However, the improvement in sperm maturation in this group when compared with cyclophosphamide-treated group shows that N-acetylcysteine could play a substantial role in germ cell survival. This follows a report by Erkkilä et al (1998) that N-acetylcysteine plays an important role in germ cell survival in human seminiferous tubules in an in-vitro study.…”

The role of N‐acetyl‐cysteine (NAC) orally daily on the sperm parameters and serum hormones in idiopathic infertile men: A systematic review and meta‐analysis of randomised controlled trials

“…Moreover, NAC plays an important role in the survival of the germ cells of human seminiferous tubules in vitro (Erkkilä et al, 1998;Oeda et al, 1997).…”

“…NAC conduces to the synthesis of glutathione (GSH) (Rushworth & Megson, 2014) and may help restore the depleted pool of GSH caused by OS and inflammation (Shimamoto et al, 2011;Wang et al, 2014). Some studies have reported that NAC had free radical scavenging activity both in vivo and in vitro (Ciftci et al, 2009;Erkkilä et al, 1998;Oeda et al, 1997). Safarinejad et al indicated that NAC orally daily can significantly improve sperm motility compared with placebo (Safarinejad & Safarinejad, 2009).…”

SLC6A8-mediated intracellular creatine accumulation enhances hypoxic breast cancer cell survival via ameliorating oxidative stress

“…The aberrantly high level of ROS has detrimental consequences on cell viability through extensive damage of DNA, proteins and organelles [29]. Antioxidant Nacetyl-L-cysteine (NAC) was considered as an important molecule of antioxidant defense for cellular resistance to exogenous stress [30,31]. Thus, antioxidant N-acetyl-Lcysteine (NAC) was employed as positive control to verify whether creatine could maintain hypoxic TNBC cell survival.…”