Abstract

Gui-A-Gra, a commercial insect powder from Gryllus bimaculatus, is registered as an edible insect by the Korean food and drug administration. The aim of this study was to investigate the effect of Gui-A-Gra on testicular damage induced by experimental left varicocele in male Sprague Dawley rats. A total of 72 rats were randomly divided into the following six groups (12 rats in each group): a normal control group (CTR), a group administrated with Gui-A-Gra 1.63 gm/kg (G1.63), a group administrated with Gui-A-Gra 6.5 gm/kg (G6.5), a varicocele (VC)-induced control group (VC), a VC-induced group administrated with Gui-A-Gra 1.63 gm/kg (VC + G1.63), and a VC-induced group administrated with Gui-A-Gra 6.5 gm/kg (VC + G6.5). Rats were administrated 1.63 or 6.5 gm/kg Gui-A-Gra once daily for 42 days. Indicators of sperm parameters, histopathology, reproductive hormones, oxidative stress, endoplasmic reticulum (ER) stress, inflammation, and mitochondrial apoptosis were analyzed to evaluate effects of Gui-A-Gra on VC-induced testicular dysfunction. Gui-A-Gra administration to VC-induced rats significantly (p < 0.05) increased sperm count and sperm motility, Johnsen score, spermatogenic cell density, serum testosterone, testicular superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase, GPx4, and steroidogenic acute regulatory protein (StAR) level. Moreover, pretreatment with Gui-A-Gra significantly (p < 0.05) decreased terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) positive cells/tubules, serum luteinizing hormone (LH), serum follicle-stimulating hormone (FSH), testicular tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), malondialdehyde (MDA), reactive oxygen species (ROS)/reactive nitrogen species (RNS) level, 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 BCL2 associated X protein: B-cell lymphoma 2 (Bax: Bcl2) ratio in VC rats. These results suggest that protective effects of Gui-A-Gra on VC-induced testicular injury might be due to its antioxidant, anti-inflammatory, and androgenic activities that might be mediated via crosstalk of oxidative stress, ER stress, and mitochondrial apoptosis pathway.

Highlights

  • IntroductionVaricocele (VC) is characterized by dilation and tortuosity of internal spermatic vein (pampiniform plexus), a network of veins that drains testicular tissues [1]

  • Varicocele (VC) is characterized by dilation and tortuosity of internal spermatic vein, a network of veins that drains testicular tissues [1]

  • Effects of GUI-A-GRA on body weight, organ weights, sperm count, and sperm motility in both vas deferens and epididymis are summarized in Tables 1 and 2

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Summary

Introduction

Varicocele (VC) is characterized by dilation and tortuosity of internal spermatic vein (pampiniform plexus), a network of veins that drains testicular tissues [1]. Adverse effects of VC on male reproduction are associated with decreased testicular volume, sperm count, sperm motility, testosterone level, and Leydig cell function and increased germ cell apoptosis [7]. It is generally believed that VC can induce an inhibition of testosterone biosynthesis, sperm chromosomal abnormalities, and elevation of reactive oxygen species (ROS) that can lead to oxidative stress and endoplasmic reticulum (ER) stress and trigger germ cell apoptosis [1,8]. VC associated infertility is correctable by surgical treatment including embolization, open scrotal or inguinal varicocelectomy, microsurgical varicocelectomy, and laparoscopic varicocelectomy [9]. Whether these operations can reverse altered semen parameters to baseline values in VC patients remains controversial [10]. Since there is no definite cure for VC-induced infertility, adjuvant therapies have been developed to assist varicocelectomy

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