Abstract
Schisandra chinensis Baillon (SC) has been utilized for its antioxidants and anti-inflammatory activities in a broad variety of medical applications. However; SC uses for improving fertility in males and related disorders with proper scientific validation remain obscure. The present study aimed to investigate the effects of SC on varicocele (VC)-induced testicular dysfunction and the potential molecular mechanism associated with VC-induced germ cell apoptosis. The male Sprague–Dawley rats were equally divided into four groups consisting of 10 rats in a normal control group (CTR), a control group administered SC 200 mg/kg (SC 200), a varicocele-induced control group (VC), and a varicocele-induced group administered SC 200 mg/kg (VC + SC 200). Rats were administrated 200 mg/kg SC once daily for 28 days after induction of varicocele rats and sham controls. At the end of the treatment period, body and reproductive organ weight, sperm parameters, histopathological damages, proinflammatory cytokines, apoptosis markers, biomarkers of oxidative stress, endoplasmic reticulum (ER) stress, and steroidogenic acute regulatory protein (StAR) were evaluated. The effects of SC extract on human sperm motility were also analyzed. SC treatment reduces VC-induced testicular dysfunction by significantly increasing testicular weight, sperm count and sperm motility, serum testosterone level, Johnsen score, spermatogenic cell density, testicular superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase level, and steroidogenic acute regulatory protein (StAR) level. Furthermore, the effects of SC on malondialdehyde (MDA) level, reactive oxygen species (ROS)/reactive nitrogen species (RNS) level, apoptotic index, serum luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels, Glucose-regulated protein-78 (Grp 78), phosphorylated c-Jun-N-terminal kinase (p-JNK), phosphorylated inositol-requiring transmembrane kinase/endoribonuclease 1α (p-IRE1α), cleaved caspase 3, and Bax:Bcl2 in VC-induced rats were significantly decreased. Treatment with SC extracts also increased sperm motility in human sperm. Our findings suggest that the SC ameliorate testicular dysfunction in VC-induced rats via crosstalk between oxidative stress, ER stress, and mitochondrial-mediated testicular germ cell apoptosis signaling pathways. SC promotes spermatogenesis by upregulating abnormal sex hormones and decreasing proinflammatory cytokines (interleukin-6; TNF-α).
Highlights
Varicocele (VC) is defined as an abnormal enlargement of the pampiniform plexus of the spermatic cord
In order to investigate protective effects of Schisandra chinensis Baillon (SC) extract on basic testicular dysfunction induced by varicocele, we established a VC-model and administrated rats with an SC extract at a dose of 200 mg/kg
There was no significant difference in body weight or reproductive organ weight among all groups, except for testis weight (Table 1)
Summary
Varicocele (VC) is defined as an abnormal enlargement of the pampiniform plexus of the spermatic cord. It is the leading cause of infertility in men [1]. Varicocelectomy is the most commonly used technique to treat VC-induced male infertility. After varicocelectomy treatment for VC-induced infertile men, studies have reported 50–80% improvement in semen parameters with a pregnancy rate of only 31–71%, indicating that varicocelectomy cannot completely restore fertility [3]. The pathophysiology of varicocele-related infertility is not completely understood yet, it is associated with multifactorial mechanisms. The mechanism of VC-induced testicular dysfunction includes increased temperature, inflammatory cytokines, oxidative stress, endoplasmic reticulum (ER) stress, hormonal imbalance, and apoptosis [5,6,7]
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