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

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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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          Most cited references31

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          Adult exposure to bisphenol A (BPA) in Wistar rats reduces sperm quality with disruption of the hypothalamic-pituitary-testicular axis.

          Reproductive physiology involves complex biological processes that can be disrupted by exposure to environmental contaminants. The effects of bisphenol A (BPA) on spermatogenesis and sperm quality is still unclear. The objective of this study was to investigate the reproductive toxicity of BPA at dosages considered to be safe (5 or 25mg BPA/kg/day). We assessed multiple sperm parameters, the relative expression of genes involved in the central regulation of the hypothalamic-pituitary-testicular axis, and the serum concentrations of testosterone, estradiol, LH and FSH. BPA exposure reduced sperm production, reserves and transit time. Significant damage to the acrosomes and the plasma membrane with reduced mitochondrial activity and increased levels of defective spermatozoa may have compromised sperm function and caused faster movement through the epididymis. BPA exposure reduced the serum concentrations of testosterone, LH and FSH and increased the concentration of estradiol. The relative gene expression revealed an increase in gonadotropin releasing hormone receptor (Gnrhr), luteinizing hormone beta (Lhb), follicle stimulating hormone beta (Fshb), estrogen receptor beta (Esr2) and androgen receptor (Ar) transcripts in the pituitary and a reduction in estrogen receptor alpha (Esr1) transcripts in the hypothalamus. In this study, we demonstrated for the first time that adult male exposure to BPA caused a reduction in sperm production and specific functional parameters. The corresponding pattern of gene expression is indicative of an attempt by the pituitary to reestablish normal levels of LH, FSH and testosterone serum concentrations. In conclusion, these data suggest that at dosages previously considered nontoxic to reproductive function, BPA compromises the spermatozoa and disrupts the hypothalamic-pituitary-gonadal axis, causing a state of hypogonadotropic hypogonadism.
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            Combination of vitamin E and clomiphene citrate in treating patients with idiopathic oligoasthenozoospermia: A prospective, randomized trial.

            The most common cause of male infertility is idiopathic oligoasthenozoospermia. Empirical medical treatment for idiopathic male infertility is still a controversial issue. The aim of this study was to evaluate any possible effects of combining vitamin E as antioxidant and clomiphene citrate as antiestrogen on spermatozoa concentration and motility in comparison to give either of medications alone in patients with idiopathic oligoasthenozoospermia. This is a comparative prospective randomized study. Ninety patients with idiopathic oligoasthenozoospermia were randomized into equally three groups: Group A: received vitamin E (400 mg/day) for 6 months. Group B: received clomiphene citrate (25 mg daily) for 6 months. Group C: received combination of both drugs in the same doses for 6 months. All patients were subjected to the following: history taking, general and genital examination, semen analysis, serum FSH, total testosterone, and scrotal duplex. Semen examination was performed according to the guidelines of (WHO, 2010), at the start of treatment and was repeated after 3 months and after 6 months of treatment. Regarding vitamin E group, there was insignificant increase in mean sperm concentration after 6 months of treatment in comparison to baseline. On the other hand, there was a significant improvement of mean sperm concentration in the other two groups after 6 months of treatment, with more significance in combination therapy group (p = 0.001). The mean total sperm motility has improved in all patients groups, in comparison to baseline, with more significance in combination therapy group. In vitamin E group, it was 28.07 ± 9.65% (p = 0.000). For those in clomiphene citrate group, was 33.33 ± 14.10% (p = 0.003) and 40.50 ± 17.54% (p = 0.000) in combination therapy group. Combining antioxidant and anti-estrogen therapy is a valid option for the treatment of a selected group of men with unexplained isolated oligoasthenozoospermia.
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              Lycopene protects against cyclosporine A-induced testicular toxicity in rats.

              Cyclosporine A (CsA)-induced direct failures in hypothalamic-pituitary-gonadal axis and Sertoli cell phagocytic function have been considered for testicular toxicity so far. It has clearly been reported that oxidative stress leads to damage in sperm functions and structure of the testis. Therefore, this study was conducted to demonstrate whether CsA causes testicular and spermatozoal toxicity associated with the oxidative stress, and to investigate the possible protective effect of lycopene against CsA-induced damages in all reproductive organs and sperm characteristics in male rats. While the daily administration of CsA at the dose 15 mg/kg for 21 days significantly decreased the seminal vesicles weight, epididymal sperm concentration, motility, testicular tissue glutathione (GSH), glutathione peroxidase (GSH-Px) and catalase (CAT), diameter of seminiferous tubules and germinal cell thickness, it increased malondialdehyde (MDA) level and abnormal sperm rates along with degeneration, necrosis, desquamative germ cells in testicular tissue. However, the CsA along with simultaneous administration of lycopene at the dose of 10mg/kg markedly ameliorated the CsA-induced all the negative changes observed in the testicular tissue, sperm parameters and oxidant/antioxidant balance. In conclusion, CsA-induced oxidative stress leads to the structural and functional damages in the testicular tissue and sperm quality of rats and, lycopene has a potential protective effect on these damages.
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                Author and article information

                Journal
                Exp Ther Med
                Exp Ther Med
                ETM
                Experimental and Therapeutic Medicine
                D.A. Spandidos
                1792-0981
                1792-1015
                January 2018
                08 November 2017
                08 November 2017
                : 15
                : 1
                : 813-821
                Affiliations
                [1 ]Department of Histology and Embryology, Jilin Medical University, Jilin, Jilin 132013, P.R. China
                [2 ]Medical Experimental Center, Jilin Medical University, Jilin, Jilin 132013, P.R. China
                [3 ]Reproductive Medicine Center of The Affiliated Hospital of Jining Medical College, Jining, Shandong 272029, P.R. China
                [4 ]Department of Urology, Affiliated Hospital of Jilin Medical University, Jilin, Jilin 132013, P.R. China
                Author notes
                Correspondence to: Professor Zhixin Li, Department of Histology and Embryology, Jilin Medical University, 5 Jilin Street, Jilin, Jilin 132013, P.R. China, E-mail: pxy19790122@ 123456163.com
                Article
                ETM-0-0-5473
                10.3892/etm.2017.5473
                5772751
                29399088
                8e7ff0bc-59ef-4917-87e0-650dbd967ae2
                Copyright: © Pan et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                : 04 May 2016
                : 31 March 2017
                Categories
                Articles

                Medicine
                new wenshen shenjing decoction,cyclosporine,testes,testosterone synthesis,cell apoptosis
                Medicine
                new wenshen shenjing decoction, cyclosporine, testes, testosterone synthesis, cell apoptosis

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