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Role of leptin and the leptin receptor in the pathogenesis of varicocele-induced testicular dysfunction.

ABSTRACT: The present study investigated the expression of leptin and its receptor in the left testis and hypothalamus of rats with varicocele and clarified their roles in the pathogenesis of varicocele?induced testicular dysfunction. A total of 40 male rats were divided randomly into four groups. Groups 1 (G1) and 3 (G3) underwent a sham operation. Groups 2 (G2) and 4 (G4) underwent operations to form a varicocele created by partial ligation of the left renal vein. G1 and G2 rats were euthanized 4 weeks after the operation while G3 and G4 rats were euthanized at 8 weeks. The expression of leptin and its receptor was analyzed by immunohistochemistry. The mRNA levels of leptin, its receptor, kisspeptin (KiSS?1), G?protein coupled receptor 54 (GPR54), gonadotropin releasing hormone (GnRH), luteinizing hormone (LH), and follicle?stimulating hormone (FSH) were measured by reverse transcription?quantitative polymerase chain reaction. Testicular spermatogenesis function and gonadal hormone levels were measured. Compared with G1 and G3, the expression of leptin and its receptor in rat testis was significantly higher in G2 and G4, respectively. Leptin expression was inversely associated with the number of sperm in the left epididymis, thickness of the seminiferous epithelium and the diameter of seminiferous tubules. The expression of leptin receptors in the hypothalamus of G2 and G4 was significantly increased compared with that in G1 and G3, respectively. The mRNA levels of KiSS?1, GPR54, GnRH, LH and FSH in G2 and G4 were significantly increased compared with that in G1 and G3, respectively. Serum testosterone levels in G2 and G4 rats were significantly lower than those in G1 and G3 rats, respectively. There was no significant difference between the serum levels of FSH, LH and leptin. These results suggest that leptin and its receptor may serve significant roles in the pathogenesis of varicocele-induced testicular dysfunction.

SUBMITTER: Zhang J

PROVIDER: S-EPMC5928662 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Role of leptin and the leptin receptor in the pathogenesis of varicocele-induced testicular dysfunction.

Zhang Jie J Jin Peng-Peng PP Gong Min M Yi Qing-Tong QT Zhu Ru-Jian RJ

Molecular medicine reports 20180315 5

The present study investigated the expression of leptin and its receptor in the left testis and hypothalamus of rats with varicocele and clarified their roles in the pathogenesis of varicocele‑induced testicular dysfunction. A total of 40 male rats were divided randomly into four groups. Groups 1 (G1) and 3 (G3) underwent a sham operation. Groups 2 (G2) and 4 (G4) underwent operations to form a varicocele created by partial ligation of the left renal vein. G1 and G2 rats were euthanized 4 weeks ...[more]

PMID: 29568885

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Project description:Background:Cisplatin (CP) is an extremely effective anticancer agent widely used to treat various cancer types, however, the potential side effects include testicular dysfunction. This study was to investigate, using a rat model of CP-induced testicular dysfunction, the protective effects of relaxin (RLN) against oxidative stress, testicular function, histological damage, spermatogenesis, germ-cell apoptosis, and sperm output, and to explore the usefulness of RLN as a potential protective drug for use with CP in chemotherapeutic treatments. Methods:Sprague-Dawley male rats were used, which were divided into three groups: sham control, CP, and CP?+?RLN. Porcine RLN (500?ng/h) or saline was infused for 5?days using an implanted osmotic mini-pump following intraperitoneal injection of CP (6?mg/kg). RLN dose was chosen based on previous studies showing that it resulted in serum relaxin levels comparable to those in rats at the middle of pregnancy. At 5?days after CP administration, samples were collected and assessment of testicular histopathology, germ-cell apoptosis, oxidative stress, lipid peroxidation, and sperm quality was performed as main measures. Results:The testicular CP model showed reduced testis weight and significantly decreased spermatogenesis scores. Additionally, CP administration induced a 4.6-fold increase in the apoptotic index associated with a significant increase in oxidative stress and upregulation of pro-apoptotic Casp3 and downregulation of anti-apoptotic Bcl2 levels, resulting in a marked reduction in sperm concentration. However, RLN administration caused a significant reduction in CP-mediated damage by attenuating oxidative stress and cell apoptosis. RLN administration efficiently scavenged ROS via the activation of SOD, CAT, and GPx and upregulation of GSH to prevent lipid peroxidation and decreased apoptosis by altering Bcl2 and Casp3 expression, thereby reducing histopathological damage and restoring spermatogenesis. Furthermore, RLN ameliorated attenuated sperm motility in the cauda epididymis resulting from CP treatment. Conclusions:This study clearly indicates that RLN exerts a protective effect against CP-induced testicular damage through attenuation of oxidative stress and suppression of apoptosis. Our findings suggest RLN as a potentially efficacious drug for use with cisplatin chemotherapy in order to ameliorate CP-induced side effects and testicular injury adversely affecting spermatogenesis, sperm quality, and oxidative-stress parameters.

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Dataset Information

Role of leptin and the leptin receptor in the pathogenesis of varicocele-induced testicular dysfunction.

Publications

Role of leptin and the leptin receptor in the pathogenesis of varicocele-induced testicular dysfunction.

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