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Background Monotropein, astragalin, and spiraeoside (MAS) are active compounds extracted from medicinal herbs; monotropein from Morinda officinalis How (Rubiaceae), astragalin (kaempferol 3-O-glucoside) from Cuscuta chinensis Lamark (Convolvulaceae) and spiraeoside from the outer scales of Allium cepa L. (Liliceae) in a ratio of 6.69:0.41:3.61. Monotropein, astragalin, and spiraeoside are well-known antioxidants, anti-inflammatory, and antinociceptive agents. The current investigation aims to study the molecular mechanism of varicocele-induced male infertility and the underlying pharmacological mechanisms of MAS. Methods Four groups were included: control (CTR), MAS 200 group (MAS 200 mg/kg), varicocele group (VC), and VC + MAS 200 group (MAS 200 mg/kg). Sprague-Dawley (SD) rats were treated with 200 mg/kg MAS or vehicle once daily for 28 days. The possible signaling mechanism and effects of MAS were measured via histological staining, immunohistochemistry, western blot, and biochemical assays. Results Parameters such as sperm motility and count, Johnsen’s scores, spermatogenic cell density, serum testosterone, testicular superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx) and expression of the steroidogenic acute regulatory protein (StAR) improved significantly in the VC + MAS 200 group compared with the VC group. MAS treatment of varicocele-induced group significantly decreased the levels of serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH), as well as testicular interleukin-6 (IL6), tumor necrosis factor-α (TNF-α), ROS/RNS, and malondialdehyde (MDA). It also decreased the apoptotic index and reduced the expression of endoplasmic reticulum (ER) protein levels (Grp78, p-IRE1α, and p-JNK) and apoptotic markers such as cleaved caspase-3 and Bax/Bcl2 ratio. Conclusion This study suggests that the crosstalk between oxidative stress, ER stress, and mitochondrial pathway mediates varicocele-induced testicular germ cell apoptosis. MAS promotes spermatogenesis in varicocele-induced SD rat, probably by decreasing cytokines (IL-6, TNF-α) levels, regulating abnormal sex hormones, and decreasing oxidative stress, ER stress, and apoptosis.

Background DA-9401 was prepared as a mixture of Chinese medicinal herb extracts from roots of Morinda officinalis How (Rubiaceae), outer scales of Allium cepa L. (Liliceae) and seeds of Cuscuta chinensis Lamark (Convolvulaceae). The present study was designed to investigate the possible protective role of DA-9401 in adriamycin (ADR)-induced testicular toxicity associated with oxidative stress, endoplasmic reticulum (ER) stress, and apoptosis. Methods Fifty healthy 8-week-old male Sprague–Dawley rats were equally divided into five groups. The first CTR group was treated with normal saline 2 ml/day by gavage. The second was treated with DA-100 (DA-9401 100 mg/kg/day). The third (ADR) group received ADR (2 mg/kg/once a week) intraperitoneally, while the combination of ADR and DA-9401 was given to the fourth ADR + DA-100 (100 mg/kg/day p.o) group and fifth ADR + DA-200 (200 mg/kg/day p.o) group. At the end of the 8-week treatment period, body weight, reproductive organ weights, fertility rate, pups per female were recorded, and serum were assayed for hormone concentrations. Tissues were subjected to semen analysis, histopathological changes, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), oxidative stress markers and expression levels of endoplasmic reticulum (ER) stress markers, apoptosis markers, tight junction protein markers, steroidogenic acute regulatory protein (StAR), cation channel of sperm (CatSper) and glycogen synthase kinase-3 (GSK-3) by western blot. Results DA-9401 administration to ADR-treated rats significantly decreased serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels, interleukin-6, TNF-α, MDA level, ROS/RNS level, ER stress response protein levels, tunnel positive cells, cleaved caspase-3, and Bax/Bcl2 ratio. Moreover, pretreatment with DA-9401 significantly increased body weight, reproductive organ weights, fertility rate, pups per female, Johnsen’s score, spermatogenic cell density, sperm count and sperm motility, serum testosterone concentration, testicular superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), tight junction protein markers, star protein level, CatSper, and GSK-3 level. Conclusions ADR treatment can markedly impair testicular function and induce testicular cell death presumably by causing significant changes in oxidative stress, ER stress, and mitochondrial pathway. DA-9401 exerts beneficial effects against oxidative stress, ER stress, and mitochondria-mediated cell death pathway in testis tissue by up-regulating expression levels of tight junction protein markers, steroidogenic acute regulatory protein, GSK-3 alpha, and cation channels of sperm. Electronic supplementary material The online version of this article (10.1186/s12935-019-0805-2) contains supplementary material, which is available to authorized users.

Introduction Icariin has been shown to improve penile hemodynamics in animal models of erectile dysfunction from cavernous nerve injury and castration. The effects of icariin on penile hemodynamics in diabetic animals remain to be determined. Transforming growth factor β1 (TGFβ1) has been implicated in the pathogenesis of diabetes-related erectile dysfunction. Aim The aim of this study was to investigate the effects of icariin in the penis of streptozotocin (STZ)-induced diabetic rat. Methods Two-month-old Sprague–Dawley male rats received one-time intraperitoneal (IP) STZ (60 mg/kg) or vehicle injection after a 16-hour fast. Three days later, the STZ-induced diabetic rats were randomly divided into four groups and were treated with daily gavage feedings of a 50:50 mix of normal saline and dimethyl sulfoxide (DMSO) or icariin dissolved in DMSO at doses of 1, 5, and 10 mg/kg for 3 months. A positive control group underwent IP injection of saline followed by daily gavage of saline/DMSO solution. Treatment was stopped 1 week prior to functional assay and euthanasia. Main Outcome Measure Penile hemodynamics was assessed by electrical stimulation of the cavernous nerves with real-time intracavernous pressure (ICP) measurement. After euthanasia, penile tissue was studied using immunohistochemistry, Western blot, and enzyme-linked immunosorbent assay (ELISA) to assess the nitric oxide-cyclic guanosine monophosphate (NO-cGMP) and TGFβ1/Smad2 signaling pathway. Results Diabetes attenuated ICP response in control animals. Untreated diabetic animals had decreased smooth muscle/collagen ratio and endothelial cell content in the corpora cavernosa; treatment with icariin partially attenuating these effects. Icariin-treated animals also had a significantly greater expression of nicotinamide adenine dinucleotide phosphate-positive nerves and the endothelial cell markers, von Willebrand factor (vWF), and platelet endothelial cell adhesion molecule-1 (PECAM). TGFβ1/Smad2 signaling pathway was down-regulated in the penis from icariin-treated models relative to what was observed in negative control animals. Conclusion Icariin treatment preserved penile hemodynamics, smooth muscle and endothelial integrity, and neuronal nitric oxide synthase expression in the penis of diabetic rats. Down-regulation of TGFβ1/Smad2 signaling pathway might mediate this effect.

The effect of unripe Rubus coreanus extract on rabbit penile corpus cavernosum (PCC) was evaluated. Penises were obtained from healthy male New Zealand white rabbits (2.5–3.0 kg). The pre-contracted penis with phenylephrine (Phe, 10 μm) was treated with various concentrations of an extract of unripe R. coreanus (0.5, 1, 2, 3 and 4 mg/mL). The change in penile tension was recorded, cyclic nucleotides in the perfusate and the PCC were measured by radioimmunoassay, and the expression of neuronal nitric oxide synthase (nNOS) and endothelial nitric oxide synthase (eNOS) in the perfused PCC were measured by western blotting. The interaction between unripe R. coreanus and sildenafil was also evaluated. The PCC relaxation induced by the extracts of R. coreanus was in a concentration-dependent manner and enhanced sildenafil-induced PCC relaxation. The perfusion of penile cavernous tissue with the unripe R. coreanus extract increased cGMP and cAMP in the tissue and in the perfusate and the expression of eNOS and nNOS in the tissue. The unripe R. coreanus extract exerts a relaxing effect on penile cavernous tissue in part by activating the NO-cGMP system and it may improve erectile dysfunction (ED), which does not completely respond to sildenafil citrate. Copyright © 2011 John Wiley & Sons, Ltd.

IntroductionThe present study introduces a newly devised in vitro penile perfusion model, which allows the measurement of changes in intracavernosum pressure (ICP), tension, and cyclic nucleotides in penile tissue in a one-step procedure.AimsWe compared the penile perfusion model with the classical penile strip chamber model to develop the new model.MethodsWe investigated the role of nitric oxide-cyclic guanosine monophosphate pathway in both systems activated by acetylcholine or electrical field stimulation (EFS). We measured cGMP (cyclic guanosine monophosphate) in the penile corpus cavernosum smooth muscle in both systems and perfusates in the penile perfusion model. We determined ICP, tension, and cGMP simultaneously in penile perfusion model during the experiments.Main Outcome MeasuresChanges of tension and cGMP in both models, and of cGMP in perfusates and of ICP in penile perfusion model.ResultsIn both systems, acetylcholine relaxed the phenylephrine-precontracted penile corpus cavernosum smooth muscle in a concentration-dependent manner. EFS decreased the tension in both models and ICP in the penile perfusion model in a frequency-dependent manner. Pretreatment with atropine, Nω nitro-L-arginine-methyl ester (L-NAME), and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) blocked the acetylcholine-induced decrease in the tension in both models and ICP in penile perfusion model. Acetylcholine increased cGMP levels in the perfusate of penile perfusion model and the changes were attenuated by tetrodotoxin (TTX), atropine, L-NAME and ODQ. EFS increased cGMP levels of the penile corpus cavernosum smooth muscle of both models and the changes were attenuated by TTX, atropine, L-NAME, and ODQ.ConclusionThe results indicated that the responses of penile strip and perfused penile tissue to acetylcholine and EFS were very similar in both models in terms of tension and cGMP levels. Furthermore, the new model has more advantages over the classical penile strip chamber model in measuring intracavernosum metabolic changes and ICP without interruption of the procedure.

Objective We evaluated long term clinical outcome in patients post corpus cavernosum-corpus spongiosum shunt (Al-Ghorab shunt) plus intracavernous tunneling (CC-CSS + ICT) for prolonged ischemic priapism (PIP). Methods Forty two patients post CC-CSS + ICT for PIP were treated in Andrology Center, Peking University First Hospital, Peking University during 2007 to 2014, then were followed up and evaluated using International Index of Erectile Function (IIEF), and quality of life (QOL) questionary form and color duplex Doppler ultrasonography (CDDU) and urinary flows. Results Thirty eight patients (90.1%) were followed up with the mean age of 41±9.2 years old and with the mean duration of follow up of 46±7.8 months. The response to PDE5i was evaluated also. All patients severe corpus cavernosum fibrosis were evaluated by CDDU without severe penile curvature and urinary dysfunction. However, all patients were suffered from erectile dysfunction with significantly decreased QOL. Only three cases (8%) were responded to PDE5i treatment, and eight cases (21%) were successfully treated by penile prosthesis implantation. Conclusions These results suggested that the CC-CSS + ICT could quickly reduce penile rigidity and pain of PIP, however, erectile dysfunction due to sever corpus carvernosum fibrosis post CC-CSS + ICT significantly influence QOL of patients and penile prosthesis implantation is a safe and effective method for treating ED for post CC-CSS + ICT.

Objective: The aim of this study was to find the mechanism that causes urethral stricture with a view to preventing its occurrence after implantation of a three-piece inflatable penile prosthesis. Methods: When implanting a three-piece inflatable penile prosthesis, we draw two longitudinal lines parallel to the long axis of the proximal cylinder and the tubing leading from each cylinder into the cavernosal space, to prevent 360 degree rotation of the cylinder. Results: From September 1993 to February 2007, a total 86 three-piece penile prosthesis implantations were carried out in 70 patients. Urethral stricture occurred in 5.8% (5/86) of the prosthesis operations. Fifteen three-piece penile prosthesis reinsertions were carried out in 17.4% (15/86) of the prosthesis recipients. Conclusions: A successful outcome was achieved in the patients who received penile implantation with the three-piece penile prosthesis that were marked with longitudinal lines. The rotation of the cylinder may cause compression on the urethra from the tubing leading from the cylinder or pump crossing over the urethra and resulting in urethral stricture. The drawing of longitudinal lines at the proximal cylinder and tubing leading from the cylinder could prevent the urethral stricture induced by tubes that are twisted by rotation of the cylinder.

To assess the role of peptides of the angiotensin (ANG) on the regulation of clitoral cavernosum tone and changes in ANG binding affinity in the rabbit with diabetes mellitus.The isometric tension measurement and in vitro autoradiography were used in sham and diabetic clitoral cavernosum.In tension study, contractility in response to ANG I, ANG II, ANG III and ANG IV was enhanced in diabetic clitoral cavernosum strips (EC50 was 67.6 +/- 27.2, 4.3 +/- 0.4, 189.3 +/- 37.3, 443.2 +/- 0.4 nM for diabetic versus 155.2 +/- 76.1, 38.3 +/- 0.1, 528.0 +/- 75.2, 616.9 +/- 69.5 nM for sham, respectively). Contractile responses to ANG II was significantly inhibited by type 1 ANG II receptor (AT1) antagonist but not by type 2 ANG II receptor (AT2) antagonist in both groups. Percentages in contractions by ANG II (1 nM) in the presence of Dup 753 decreased significantly 36.2 +/- 4.6 to 6.3 +/- 2.4% in sham and 56.1 +/- 7.7 to 6.0 +/- 4.8% in diabetic group. The binding affinities were enhanced in diabetic clitoral cavernosum for ANG II (dissociation constant, 4.9 +/- 1.0 for sham versus 0.9 +/- 0.2 nM for diabetic) and for ANG I, ANG III, and ANG IV (inhibitory constant, 28.6 +/- 1.5, 398.7 +/- 157.2, and 3966.5 +/- 1524.1 nM for sham versus 20.6 +/- 5.7, 78.5 +/- 23.7, and 1098.7 +/- 195.5 nM, for diabetic, respectively, all p0.05). Sensitivities of AT1 and AT2 receptors to ANG II enhanced in diabetic than sham clitoral cavernosum tissue.This results suggest that the contractile responses to all four ANG peptides are enhanced in the diabetic clitoral cavernosum. Enhancement of contractility in diabetic clitoral cavernosum may be related to the increased affinity to ANG II receptors for ANG peptides.

To compare and analyze semen quality improvement between the patients with microscopic varicocelectomy and laparoscopic varicocelectomy.A total of 291 patients with varicocele were included in this study, of whom 176 underwent microscopic varicocelectomy and 115 laparoscopic varicocelectomy. The improvement rates of semen quality and pregnancy rates between the two groups were compared.The improvement rate of sperm density in microscopic group was significantly higher than that of laparoscopic group (87.6% vs. 73.7%, P = 0.006). Spouse pregnancy rate of microscopic group was significantly higher than that of laparoscopic group (45.4% vs. 30.3%, P = 0.017).The effect of microscopic varicocelectomy was superior to that of laparoscopic varicocelectomy.

To evaluate the efficacy of microsurgical vasectomy reversal on patients after vasectomy.In the study, 41 patients after vasectomy were admitted for microsurgical vasectomy reversal. The mean (range) age was 45 (29 to 66) years for the men. The mean duration of obstruction was 12 years. All the patients were seen by the surgeon for a complete history and physical examination. Semen analyses proved azoopermia, and their serum levels of sexual hormone were normal. They were all offered scrotal exploration. Microvasovasostomy was performed if the sperm was found in the material coming from the proximal vas lumen. The decision for microvasoepididymostomy was made during surgery, if the fluid was creamy, containing only debris or there was no fluid whatsoever when the vas was milked toward the cut end. Microvasovasostomy was performed in 40 patients, of whom 6 were with lateral microvasoepididymostomy and 1 with bilateral microvasoepididymostomy. The initial semen analysis was then done after usually 3 months postoperatively. Patency was arbitrarily defined as10 000 sperm/mL in ejaculate in at least one semen analysis after surgery. Postoperative patency rate and postoperative impregnation rate were followed.The 41 patients were followed up for 3 to 72 months, and 5 cases were lost. In the 28 patients who had obstructions for less than 15 years, 3 were lost. Sperm was found by semen analysis in 21 patients. Their sperm density was 2×10(6) to 46×10(6) sperms/mL and motility was 0% to 60%. The semen analysis revealed azoospermia in 2 patients after 12 months, who were advised to undergo intracytoplasmic sperm injection. Natural conception occurred in 6 patients followed for more than 12 months. The overall patency rate was 84% (21/25). Among the patients with a follow-up of6 months, the natural paternity rate was 29% (6/21). In the 13 patients who had obstructions for more than 15 years, 2 were lost. The patency and pregnancy rates were 64% (7/11) and 14% (1/7) respectively. Their sperm density was 0.02×10(6) to 30× 10(6) sperms/mL and motility was 0% to 43%.Microsurgical vasectomy reversal is an effective method to treat vasal obstruction due to vasectomy. The patency and pregnancy rates are related to the time of vasectomy. The patency and pregnancy rates are higher in patients with obstruction for less than 15 years than those for more than 15 years.

To evaluate the effect of daily low-dose tadalafil on erectile dysfunction (ED) induced by pelvic fracture urethral disruption (PFUD).This study included 46 cases of PFUD-induced ED treated from Jan 2008 to Dec 2011. The patients were aged 33.9 +/- 7.2 years (range 25 -51 yr), and the interval between injury and treatment was 19.6 +/- 12.7 months (range 3 - 72 mo), all with normal erectile function before PFUD. Based on the nocturnal penile tumescence and rigidity (NPTR) recorded by erectometry without medication of phosphodiesterase type 5 inhibitor (PDE-5I), the patients were divided into an abnormal nocturnal erection group and a non-nocturnal erection group, and treated with tadalafil 10 mg once daily for 3 months. The therapeutic effect was evaluated by IIEF-5 scores and the rate of yes responses to questions 2 and 3 of the Sexual Encounter Profile (SEP).Totally 38 (82.6%) of the patients accomplished the treatment and follow-up, 26 (68.4%) in the abnormal nocturnal erection group and 12 (31.6%) in the non-nocturnal erection group. After 3 months of daily tadalafil treatment at 10 mg, the IIEF-5 scores were significantly improved in the abnormal nocturnal erection group than in the non-nocturnal erection group (P0.05), and the rate of yes responses to SEP2 and SEP3 was remarkably higher in the former than in the latter (76.9% vs 41.7% and 65.4% vs 25.0%, P0.05).Daily low-dose tadalafil can effectively improve the erectile function of PFUD-induced ED patients, particularly in those with nocturnal erection.

Objective Cisplatin causes male infertility but the exact mechanism has not been clarified, yet. MOTILIPERM has been implicated in alleviation of infertility in Sprague-Dawley rats caused by cisplatin. We evaluated recovery effect of MOTILIPERM on cisplatin (CIS)-induced testicular toxicity in Sprague-Dawley rats. Methods Five groups were included. The groups are control (CTR), CTR + MOTILIPERM 200 mg/kg/day per oral, CIS 10 mg/kg i.v., CIS 10 mg/kg + MOTILIPERM 100 mg/kg/day, CIS 10 mg/kg + MOTILIPERM 200 mg/kg/day. CIS 10 mg/kg i.v. single dose was given before 100 or 200 mg/kg MOTILIPERM per oral daily for 28 days. Body and genital organs weight, epididymis sperm count, sperm motility, sperm apoptosis, testosterone level, MDA of testis tissue, spermatogenic cell density, and Johnsen’s score were evaluated. Steroidogenic acute regulatory (StAR) protein, and Glucose-regulated protein-78 (GRP-78), phosphorylated inositol-requiring transmembrane kinase/endoribonuclease 1 (ire1) and phosphorylated c-jun-N-terminal kinase (p-JNK) were quantitated by western blot to show its signaling pathway. Results The body weight was decreased significantly in CIS 10 mg/kg, CIS 10 mg/kg + MOTILIPERM 100 mg/kg/day, CIS 10 mg/kg + MOTILIPERM 200 mg/kg/day compared with CTR (P

To investigate the clinical efficacy and patient and partner's satisfaction with penile prosthesis implantation (PPI) for treating Chinese patients with severe erectile dysfunction (SED).One hundred and sixty-eight SED patients were successfully treated by PPI from July 2000 to June 2010. Of the 146 (86.9%) patients who had been followed up over 6 months post-operation, 36 (24.7%) had been implanted with one piece malleable prosthesis (AMS650) and 110 (75.3%) with three piece inflatable prosthesis (AMS700CXM).All the patients had been followed up by using international index of erectile dysfunction (IIEF5), Quality of Life Score (QOL) for evaluating clinical efficacy and using Visual Analogue Scale (VAS) for evaluating patient and partner's satisfaction and the duration of the follow-up was 6 to 119 months.The mean age of patients was 35.9+/-12.1 years(20 to 75 years), All the operations were successful and sexual intercourse with PPI was performed post 4 to 6 weeks without severe complications like infection and erosion. The prosthesis survive rate and frequent sexual intercourse rate were 98.6% and 87.7% respectively. IIEF5 scores pre and post PPI were 6.3+/- 1.7 and 21.3+/-1.6 respectively,the QOL scores pre and post PPI were 5.1+/-0.9 and 1.5+/-0.5 respectively, and both of them showed significant improvement (P0.01). As for VAS, the patient and partner's overall satisfaction rates were 92.5% and 90.4% respectively. Moreover, better satisfaction was showed with AMS700CXM as compared with AMS650 (P0.05) in patients with SED.PPI is the safe and effective treatment option for Chinese patients with SED. The AMS700CXM penile prosthesis is better than AMS650 for patients' overall satisfaction.

Introduction. Simultaneous urethral repair and reimplantation of penile prosthesis in a patient with urethral stricture induced by rotated tubing of a three piece penile prosthesis has not been reported yet. Aim. The aim of this study was to present our experience, which overcame severe urethral stricture induced by penile prosthesis implantation. Main Outcome Measure. Uroflowmetry, voding cystourethrogram, function of prosthesis, and complications. Methods. We performed one-stage urethroplasty with pedicle island of penile skin and reimplantation of Titan penile prosthesis without abnormal rotation of the cylinder. Results. The patient voided very well, and the prosthesis worked very well without complications. Conclusion. One-stage urethroplasty with pedicle island of penile skin and reimplantation of a three-piece penile prosthesis in simultaneous stage may be another choice to treat the long-segment urethral stricture occurred by

OBJECTIVE To evaluate prospectively and compare the clinical response and the change in nucleotides correlating with haemodynamic changes in the cavernosal arteries after an intracavernosal injection (ICI) with vasoactive agents with or without oral sildenafil in men with erectile dysfunction (ED). PATIENTS AND METHODS In all, 80 patients with ED were prospectively evaluated by clinical assessments, measuring nucleotides in blood plasma and haemodynamics in cavernosal arteries. All patients had colour Doppler ultrasonography (CDU) twice with an interval of 5 h. First, each patient had CDU after ICI with trimix (0.25 mL) or prostaglandin E1 (PGE1, 5 µg), and the second CDU was after ICI trimix given 1 h after oral placebo (group I), sildenafil 25 mg (group II) or 100 mg (group III) and after ICI with PGE1 at 1 h after oral placebo (group IV) or 100 mg sildenafil (group V). Levels of cGMP and cAMP in peripheral venous and penile cavernosal blood plasma were measured at 15 min after ICI. RESULTS The mean peak systolic velocity (PSV) at 5, 10, 15 min, and resistive index at 10 min in the second CDU after ICI with trimix, were significantly increased in group III. The mean (sem) levels of cavernosal cGMP were significantly increased in group III and V, from 1130.1 (313.5) to 2056.7 (580.4) and 1017.0 (214.2) to 1905.2 (915.0) fmol/mL, respectively. cAMP was significantly increased in group V, from 9533.1 (2068.4) to 12150 (3684.2) fmol/mL. CONCLUSIONS The haemodynamic changes and cGMP and cAMP production in the cavernosum were improved by trimix plus sildenafil more than with than PGE1 plus sildenafil or one ICI with trimix or PGE1. The results suggest that ICI with trimix and sildenafil is the best combination for a pharmacological erection test.