Protective effects of new Wenshen Shengjing Decoction on cyclosporine‑induced impairment of testosterone synthesis and spermatogenic apoptosis

Pan,Xiaoyan; Wang,Xiyan; Wang,Xuenan; Zhang,Wansheng; Sun,Zhanxuan; Liang,Xuanxuan; Zhang,Xue; Li,Wenjun; Li,Zhixin

doi:10.3892/etm.2017.5473

Protective effects of new Wenshen Shengjing Decoction on cyclosporine‑induced impairment of testosterone synthesis and spermatogenic apoptosis

Authors:
- Xiaoyan Pan
- Xiyan Wang
- Xuenan Wang
- Wansheng Zhang
- Zhanxuan Sun
- Xuanxuan Liang
- Xue Zhang
- Wenjun Li
- Zhixin Li
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Affiliations: Department of Histology and Embryology, Jilin Medical University, Jilin, Jilin 132013, P.R. China, Medical Experimental Center, Jilin Medical University, Jilin, Jilin 132013, P.R. China, Reproductive Medicine Center of The Affiliated Hospital of Jining Medical College, Jining, Shandong 272029, P.R. China, Department of Urology, Affiliated Hospital of Jilin Medical University, Jilin, Jilin 132013, P.R. China
Published online on: November 8, 2017 https://doi.org/10.3892/etm.2017.5473
Pages: 813-821
Copyright: © Pan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The aim of the present study was to investigate the potential protective effects of new Wenshen Shengjing Decoction (new WSSJD; including Cornu Cervi Nippon Parvum, Panax ginseng, Cynomorium songaricum, Cistanche deserticola, Radix Astragali, Epimedium brevicornum and Angelica sinensis) on cyclosporine‑induced impairment of testosterone synthesis and spermatogenic apoptosis in mice. A total of 90 adult male Kunming mice were divided into the following 6 groups: Control (no intervention), dimethylsulfoxide (DMSO; received only DMSO), cyclosporine A (CsA), clomifene citrate (CC; CsA + CC, 15 mg/kg/day), WSSJD (CsA + WSSJD, crude drug 12 g/kg/day) and new WSSJD (CsA + new WSSJD, crude drug 12 g/kg/day). All mice were treated for 30 days via oral gavage. The testes were subsequently fixed and stained with hematoxylin & eosin to assess the development of seminiferous epithelia. Immunohistochemical techniques were used to detect the expression of luteinizing hormone receptor (LHR) and P450 side chain cleavage (P450scc) in testicular Leydig cells. In addition, the apoptosis of spermatogenic cells in the testes was detected using a terminal dexynucleotidyl transferase‑mediated dUTP nick‑end labeling assay, and flow cytometry was used to analyze the survival rate and early apoptosis of sperm in the epididymis. Compared with the CsA and CC groups, new WSSJD administration significantly increased levels of serum testosterone and the expressions of LHR and P450scc in testicular Leydig cells (P<0.05), while the apoptosis of spermatogenic cells in the seminiferous tubules and early apoptosis of mature sperm were significantly decreased (P<0.05). These results suggest that new WSSJD may ameliorate CsA‑induced spermatogenic damage in male mice by enhancing testosterone synthesis and the secretion of testicular Leydig cells, and by reducing the apoptosis of spermatogenic cells.

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1	Pedersen M and Seetharam A: Infections after orthotopic liver transplantation. J Clin Exp Hepatol. 4:347–360. 2014. View Article : Google Scholar : PubMed/NCBI
2	Vora GK and Ciolino JB: Corneal allograft reaction associated with nonocular inflammation. Digit J Ophthalmol. 20:29–31. 2014.PubMed/NCBI
3	De Pasquale C, Veroux M, Indelicato L, Sinagra N, Giaquinta A, Fornaro M, Veroux P and Pistorio ML: Psychopathological aspects of kidney transplantation: Efficacy of a multidisciplinary team. World J Transplant. 4:267–275. 2014. View Article : Google Scholar : PubMed/NCBI
4	El-Gowelli HM and El-Mas MM: Central modulation of cyclosporine-induced hypertension. Naunyn Schmiedebergs Arch Pharmacol. 388:351–361. 2015. View Article : Google Scholar : PubMed/NCBI
5	Eid MM, Abdel-Hamid IA, Sobh MA and el-Saied MA: Assessment of sperm motion characteristics in infertile renal transplant recipients using computerized analysis. Int J Androl. 19:338–344. 1996. View Article : Google Scholar : PubMed/NCBI
6	Zahra A, Gholamreza N, Farokhi F and Shalizar Jalali A: Attenuation of cyclosporine-induced sperm impairment and embryotoxicity by crataegus monogyna fruit aqueous extract. Cell J. 15:198–205. 2013.PubMed/NCBI
7	He Z, Qiu J, Li J, Zhao D, Chen G and Chen L: Long-term effects of conversion from cyclosporine to rapamycin on testicular function and morphology in a rat transplantation model. Transplant Proc. 45:pp. 763–769. 2013; View Article : Google Scholar : PubMed/NCBI
8	Ali RB, Klouz A, Boubaker S, Lakhal M and Belkahia C: An animal model of testicular toxicity by cyclosporine: Evaluation and protection. Fundam Clin Pharmacol. 23:241–246. 2009. View Article : Google Scholar : PubMed/NCBI
9	Seethalakshmi L, Flores C, Malhotra RK, Pallias JD, Tharakan D, Khauli RB and Menon M: The mechanism of cyclosporine's action in the inhibition of testosterone biosynthesis by rat Leydig cells in vitro. Transplantation. 53:190–195. 1992. View Article : Google Scholar : PubMed/NCBI
10	Seethalakshmi L, Flores C, Carboni AA and Menon M: Quantitative maintenance of spermatogenesis in cyclosporine-treated rats by exogenous administration of testosterone propionate. J Androl. 11:491–497. 1990.PubMed/NCBI
11	Pan XY, Wang XY, Wang XN, Sun ZX, Wang D, Wang X, Yang YY and Li ZX: Effects of ‘Wenshen Shengjing Decoction’ on cyclophosphamide induced spermatogenic cell apoptosis and histone H3K9 dimethylation. Shanghai Zhong Yi Yao Za Zhi. 48:82–86. 2014.(In Chinese).
12	Xu ZH, Li SF, Wang JY, Zhou R and Tian SJ: Extraction of sex hormone from antler velvet with supercritical CO2. Zhongguo Zhong Yao Za Zhi. 32:2000–2003. 2007.(In Chinese). PubMed/NCBI
13	Zhao LP, Xu Z, Zhang M, Sun HC and Tang F: Effects of Fructus Lycii and Radix astragali on the function of sertoli cells in rat testes. Zhonghua Nan Ke Xue. 13:82–86. 2007.(In Chinese). PubMed/NCBI
14	Xu L, Liu XH and Zhang L: Effects of total ginsenosides on the NO NOS and total antioxygen capacity in the testis of mouse. Acta Academiae Medicinae CPAPF. 5:507–508. 2006.(In Chinese).
15	Patel DP, Brant WO, Myers JB, Presson AP, Johnstone EB, Dorais JA, Aston KI, Carrell DT and Hotaling JM: The safety and efficacy of clomiphene citrate in hypoandrogenic and subfertile men. Int J Impot Res. 27:221–224. 2015. View Article : Google Scholar : PubMed/NCBI
16	ElSheikh MG, Hosny MB, Elshenoufy A, Elghamrawi H, Fayad A and Abdelrahman S: Combination of vitamin E and clomiphene citrate in treating patients with idiopathic oligoasthenozoospermia: A prospective, randomized trial. Andrology. 3:864–867. 2015. View Article : Google Scholar : PubMed/NCBI
17	Wang R, Xu L, Zhang WX, Wu YF, Shi JH and Zhang YX: Shengjing Granule: An Effective Chinese Medicine for Spermatogenic Disturbance in Mice. Zhonghua Nan Ke Xue. 14:1046–1049. 2008.(In Chinese). PubMed/NCBI
18	Fan BT: Chinese Medicine Pharmacy. Shanghai Science and Technology Press; 12. pp. 62–68. 1997, (In Chinese).
19	Zhang J, Li H, Lu L, Yan L, Yang X, Shi Z and Li D: The Yiqi and Yangyin Formula ameliorates injury to the hematopoietic system induced by total body irradiation. J Radiat Res. 58:1–7. 2017. View Article : Google Scholar : PubMed/NCBI
20	Minami M, Konishi T, Jiang Z, Arai T and Makino T: Effect of Shin'iseihaito on murine allergic reaction induced by nasal sensitization. J Tradit Complement Med. 6:252–256. 2015. View Article : Google Scholar : PubMed/NCBI
21	Rong R, Li RR, Hou YB, Li J, Ding JX, Zhang CB and Yang Y: Mahuang-xixin-fuzi decoction reduces the infection of influenza a virus in kidney-yang deficiency syndrome mice. J Ethnopharmacol. 192:217–224. 2016. View Article : Google Scholar : PubMed/NCBI
22	Johnsen SG: Testicular biopsy score count-a method for registration of spermatogenesis in human testes: Normal values and results in 335 hypogonadal males. Hormones. 1:2–25. 1970.PubMed/NCBI
23	Mays-Hoopes LL, Bolen J, Riggs AD and Singer-Sam J: Preparation of spermatogonia, spermatocytes, and round spermatids for analysis of gene expression using fluorescence-activated cell sorting. Biol Reprod. 53:1003–1011. 1995. View Article : Google Scholar : PubMed/NCBI
24	Xu LG: Influence of cyclosporin A on the semen parameters of the patients after renal transplantation. J Clin Urol. 20:603–605. 2005.
25	Pintus E, Ros-Santaella JL and Garde JJ: Beyond testis size: Links between spermatogenesis and sperm traits in a seasonal breeding mammal. PLoS One. 10:e01392402015. View Article : Google Scholar : PubMed/NCBI
26	Monteiro JC, Predes FS, Matta SL and Dolder H: Heteropterys aphrodisiaca infusion reduces the collateral effects of cyclosporine A on the testis. Anat Rec (Hoboken). 291:809–817. 2008. View Article : Google Scholar : PubMed/NCBI
27	Oseko F, Note S, Morikawa K, Endo J, Taniguchi A and Imura H: Influence of chronic hyperprolactinemia induced by sulpiride on the hypothalamo-pituitary-testicular axis in normal men. Fertil Steril. 44:106–111. 1985. View Article : Google Scholar : PubMed/NCBI
28	Wisniewski P, Romano RM, Kizys MM, Oliveira KC, Kasamatsu T, Giannocco G, Chiamolera MI, Dias-da-Silva MR and Romano MA: Adult exposure to bisphenol A (BPA) in Wistar rats reduces sperm quality with disruption of the hypothalamic-pituitary-testicular axis. Toxicology. 329:1–9. 2015. View Article : Google Scholar : PubMed/NCBI
29	Krueger BA, Trakshel GM, Sluss PM and Maines MD: Cyclosporin-mediated depression of luteinizing hormone receptors and heme biosynthesis in rat testes: A possible mechanism for decrease in serum testosterone. Endocrinology. 129:2647–2654. 1991. View Article : Google Scholar : PubMed/NCBI
30	Nolan CJ and Payne AH: Genotype at the P450scc locus determines differences in the amount of P450scc protein and maximal testosterone production in mouse Leydig cells. Mol Endocrinol. 4:1459–1464. 1990. View Article : Google Scholar : PubMed/NCBI
31	Türk G, Ateşşahin A, Sönmez M, Yüce A and Ceribaşi AO: Lycopene protects against cyclosporine A-induced testicular toxicity in rats. Theriogenology. 67:778–785. 2007. View Article : Google Scholar : PubMed/NCBI
32	Türk G, Sönmez M, Ceribaşi AO, Yüce A and Ateşşahin A: Attenuation of cyclosporine A-induced testicular and spermatozoal damages associated with oxidative stress by ellagic acid. Int Immunopharmacol. 10:177–182. 2010. View Article : Google Scholar : PubMed/NCBI