Improvement of Sperm parameters and Hormonal Receptor Expression in a Rat Model of Testicular Hypoxia Treated with N-acetylcysteine Running title: N-acetylcysteine Improves Sperm Parameters

Testicular tissue hypoxia is a state in which tissues do not receive enough oxygen to meet their demand. One disease known to cause this hypoxic condition is varicocele (VCL), which can negatively impact the testicles and lead to poor sperm quality. Previous research has indicated that antioxidants play a significant role in protecting against the damage resulting from hypoxia. This study aims to identify the potential antioxidant properties of N-acetylcysteine (NAC) on sperm characteristics and hormonal receptor expression within the testes of adult male Wistar rats. The study involved 32 rats randomly assigned to four groups: Sham (control), Varicocele-induced Hypoxia (Hypo), Hypoxia with NAC treatment (Hypo + NAC), and NAC treatment (NAC). The investigation measured serum testosterone, LH, and FSH levels, and evaluated sperm characteristics, histological features, and hormonal gene receptors across the groups. Analysis of the Hypoxia group showed a remarkable increase in serum FSH and LH levels compared to the Sham group (P < 0.05). Hypoxia led to deterioration in sperm quality, testosterone levels, number of germ cells, and hormonal receptor-related genes (P < 0.05). Importantly, NAC treatment improved male fertility by increasing sperm quality and protecting testicular tissues against hypoxia induced by varicocele in the rats.The present study suggests the potential for using NAC to prevent testicular tissue damage caused by testicular hypoxia.