Hematoma or “Partial Priapism” in the Proximal Part of the Corpus Cavernosum

Introduction“Partial priapism” is a rare disorder. Therapy is controversial in literature.AimTo show that conservative treatment leads to a full functional recovery of this condition.MethodsThis report describes a case of a hematoma or “partial priapism” in the proximal part of the right corpus cavernosum.ResultsComplete functional recovery after conservative treatment with nonsteroidal anti‐inflammatory drugs.Conclusion“Partial priapism” probably represents a hematoma in the interstitium of the proximal part of the corpus cavernosum. Conservative treatment is advised. Kropman RF and Schipper J. Hematoma or “partial priapism” in the proximal part of the corpus cavernosum. J Sex Med 2014;11:2618–2622.     

Penile Histomorphometrical Evaluation in Hypertensive Rats Treated with Sildenafil or Enalapril Alone or in Combination: A Comparison with Normotensive and Untreated Hypertensive Rats

IntroductionErectile dysfunction (ED) is frequently associated to hypertension and antihypertensive drugs; however, the penile morphological aspects on these situations are poorly known.AimEvaluate the penile morphology of untreated hypertensive rats and rats treated with enalapril or sildenafil alone or in combination to verify the hypothesis that morphological alterations promoted by hypertension on corpus cavernosum could be ameliorated by the use of angiotensin-converting enzyme inhibitors and/or phosphodiesterase type 5 inhibitors.MethodsFifty male rats were assigned into five groups: normotensive rats, untreated spontaneously hypertensive rats (SHRs), and SHR treated with enalapril or sildenafil alone or in combination. Blood pressure was measured weekly. At the conclusion of the study, the rats were euthanized, and their penises were collected for histomorphometrical analysis.Main Outcome MeasuresThe cross-sectional areas of the penis, tunica albuginea, and corpus cavernosum were measured. The density of the corpus cavernosum structures was quantified.ResultsBoth groups of SHR rats treated with enalapril became normotensive. Untreated SHR showed no difference in penile and cavernosal cross-sectional area compared with normotensive rats; however, those rats treated with enalapril or sildenafil alone demonstrated an increase in these parameters. Rats receiving combination therapy showed no cross-sectional area differences compared with normotensive rats. Cavernosal connective tissue density was increased, while the sinusoidal spaces were diminished in untreated SHR. All treatments were effective in maintaining connective tissue density in comparison with normotensive animals. Cavernosal smooth muscle density was similar in all groups, with the exception of the combination therapy group, which demonstrated a reduction in smooth muscle.ConclusionsHypertension promoted structural alterations in the corpus cavernosum that may be related to ED. Enalapril- and sildenafil-treated animals had preservation of normal corpus cavernosum structure and an increase in penile and cavernosal cross-sectional area. The combination of these drugs showed less benefit than individual use. Felix-Patrício B, Medeiros JL, Jr, De Souza DB, Costa WS, and Sampaio FJB. Penile histomorphometrical evaluation in hypertensive rats treated with sildenafil or enalapril alone or in combination: A comparison with normotensive and untreated hypertensive rats. J Sex Med 2015;12:39–47.     

Tissue engineering for penile surgery: comparative study of noncellular and cell-seeded synthetic grafts for tunica albuginea replacement

IntroductionSurgical treatment outcomes in Peyronie's disease remain controversial because of high rates of recurrence.AimThe aim of this study was to engineer in vitro a new type of tunica albuginea (TA) autologous graft obtained by culture of autologous fibroblast on a polyglycolic acid (PGA) scaffold. This engineering graft was compared with PGA with morphological and functional outcomes for TA replacement, 4 months after graft upon corpus cavernosum in a rat model.MethodsThirty‐nine Sprague Dawley adult male rats were divided into four groups: (i) control group (C) with resection and resuture of a 5 mm long and 2 mm large piece of original TA; (ii) PGA scaffold group (P) with the same resection of TA and suture of PGA scaffold; (iii) autologous fibroblast‐seeded on PGA scaffold graft after resection of the same piece of TA (F + P); and (iv) sham group for functional and histological comparison.Main Outcome MeasureThe main outcome measure was assessment of graft size variation at 4 months and comparison between the three test groups. The secondary objective is assessment of erectile function by measuring erectile response to cavernous nerve electrical stimulation in each group.ResultsAt 4 months, there was a significant difference in graft area retraction between the groups (P = 0.0081) with higher retraction in P group vs. in C or F + P groups. Erectile response to cavernous nerve stimulation significantly differed between the groups and was sham equivalent to C equivalent to F + P superior to P group.Conclusions.This study provides experimental evidence for the feasibility and the functionality of fibroblast‐seeded scaffold compared with acellular graft for TA replacement. Ferretti L, Giuliani M, Bessède T, Qiu X, Zhang H, Alsaid B, Durrbach A, Giuliano F, Benoit G, and Droupy S. Tissue engineering for penile surgery: Comparative study of noncellular and cell‐seeded synthetic grafts for tunica albuginea replacement. J Sex Med 2012;9:625–631.     

Erectile Dysfunction and Altered Contribution of KCa1.1 and KCa2.3 Channels in the Penile Tissue of Type-2 Diabetic db/db Mice

BackgroundActivation of endothelial small conductance calcium-activated K⁺ channels (KCa2.3) and intermediate conductance calcium-activated K⁺ channels (KCa3.1) leads to vascular relaxation. We found endothelial KCa2.3 down-regulation in the corpus cavernosum diminishes erectile function.AimWe hypothesized that in type-2 diabetic mice, the function of KCa2.3 and KCa1.1 channels is impaired in erectile tissue.MethodsErectile function was measured, and corpus cavernosum strips were mounted for functional studies and processed for qPCR and immunoblotting.OutcomesEffects of type 2 diabetes on erectile function, expression and function of calcium-activated potassium channels.ResultsIn anesthetized diabetic db/db mice, erectile function was markedly decreased compared to non-diabetic heterozygous db/+ mice, and the impairment was even more pronounced compared to normal C57BL/6 mice. qPCR revealed KCa2.3 and KCa1.1α channel expressions were upregulated in corpus cavernosum from db/db mice. Immunoblotting showed down-regulation of KCa2.3 channels in the corpus cavernosum from db/db mice. Acetylcholine relaxations were impaired while relaxations induced by the nitric oxide, donor SNP were unaltered in corpus cavernosum from db/db compared to C57BL/6 and db/+ mice. Apamin, a blocker of KCa2 channels, inhibited acetylcholine relaxation in corpus cavernosum from all experimental groups. In the presence of apamin, acetylcholine relaxation was markedly decreased in corpus cavernosum from db/db vs C57BL/6 and db/+ mice. An opener of KCa2 and KCa3.1 channels, NS309, potentiated acetylcholine relaxations in corpus cavernosum from db/+ and db/db mice. Iberiotoxin, a blocker of KCa1.1 channels, inhibited acetylcholine relaxation in corpus cavernosum from db/+ mice, while there was no effect in tissue from db/db mice.Clinical TranslationErectile function in diabetic db/db mice was severely affected compared to heterozygous and control mice, findings suggesting the non-diabetic db/+ and diabetic db/db mice for translational purpose can be used for drug testing on, respectively, moderate and severe erectile dysfunction. The altered expressions and impaired acetylcholine relaxation in the presence of apamin compared to C57BL/6 mice may suggest decreased KCa1.1 channel function may underpin impaired endothelium-dependent relaxation and erectile dysfunction in diabetic db/db mice.Strengths & LimitationsThe present study provides a mouse model for type 2 diabetes to test moderate and severe erectile dysfunction drugs. Decreased KCa1.1 channel function contributes to erectile dysfunction, and it is a limitation that it is not supported by electrophysiological measurements.ConclusionOur results suggest that the contribution of iberiotoxin-sensitive KCa1.1 channels to relaxation is reduced in the corpus cavernosum, while apamin-sensitive KCa2.3 channels appear upregulated. The impaired KCa1.1 channel function may contribute to the impaired erectile function in diabetic db/db mice.Comerma-Steffensen S, Prat-Duran J, Mogensen S, et al. Erectile Dysfunction and Altered Contribution of KCa1.1 and KCa2.3 Channels in the Penile Tissue of Type-2 Diabetic db/db Mice. J Sex Med 2022;19:697–710.     

The Role of Chloride Channels in Rat Corpus Cavernosum: In Vivo Study

IntroductionRecent studies have identified the existence of outward, depolarizing chloride currents in isolated rat, rabbit, and human corpus cavernosum muscle cells. However, few articles have demonstrated the functional role of chloride channels in vivo in corpus cavernosum smooth muscle.AimTo investigate the role of calcium-dependent chloride channels in erectile function of rat corpus cavernosum smooth muscle.MethodsAdult male Wistar rats were used to perform an in vivo study in a rat model of erection. Both crura of the rats were isolated to in order to record intracavernosal pressure (ICP) during basal conditions and electrical stimulation of erection, with and without intracorporeal injection of norepinephrine, chloride transport inhibitors, and chloride channel blockers.Main Outcome MeasureICP.ResultsICP increased as the amplitude of electrical stimulation increased, and decreased in a dose-dependent manner (during electrical stimulation) as norepinephrine injection strength increased. Injection into the corpus cavernosum of the Cl^- channel blockers, niflumic acid, anthracene-9-carboxylic acid, and 4,4′-diisothiocyano-2,2′-stilbene-disulfonic acid increased ICP. Injection into the corpus cavernosum of the Cl^- channel transport inhibitors bumetanide, ethacrynic acid, and HCO₃-free 4-(2-hydroxyethyl )-1-1- piperazine ethanesulphonic acid buffer, and also increase the ICP. The effects of both Cl^- channel blockers and Cl^- channel transport inhibitors on ICP were concentration-dependent.ConclusionsOur findings suggest that chloride channels play an important role in the regulation of corpus cavernous smooth muscle tone in vivo. Chung S-D, Kuo Y-C, Liu S-P, Chang H-C, Yu H-J, and Hsieh J-T. The role of chloride channels in rat corpus cavernosum: In vivo study. J Sex Med 2009;6:708–716.     

An Increased Arginase Activity Is Associated with Corpus Cavernosum Impairment Induced by Hypercholesterolemia

IntroductionHypercholesterolemia is a prevalent risk factor for the development of erectile dysfunction (ED), mostly due to an increase in oxidative stress and impaired nitric oxide (NO) bioavailability within the penis. Arginase is an enzyme that shares the common substrate L‐arginine with NO synthase. Augmented arginase activity reduces NO production and is associated with ED development. However, the contribution of arginase hyperactivity in hypercholesterolemia‐induced ED is unknown.AimIn the present study, we investigated the activity and role of arginase in the corpus cavernosum of hypercholesterolemic mice.MethodsApolipoprotein E (ApoE) gene‐deleted mice fed with a Western‐type diet for 11 weeks were treated with the selective arginase inhibitor, N‐ω‐Hydroxy‐L‐norarginine (NOHA), or vehicle (saline 0.9%) during the last 9 weeks. Arginase activity and expression were measured in penis protein extraction. Reactive oxygen species (ROS) content within the corpus cavernosum was measured by dihydroethidium staining. Functional in vitro studies were performed using cavernosal strips mounted in an isometric organ bath to evaluate NO production.Main Outcome MeasureArginase activity and its role in modulating NO and ROS production within the corpus cavernosum of hypercholesterolemic mice is the main outcome measure.ResultsTotal arginase activity and arginase type II protein expression were increased in hypercholesterolemic mice compared with wild‐type mice. The long‐term treatment with NOHA normalized this alteration. Moreover, pharmacological arginase inhibition by NOHA attenuated the augmented ROS production within the corpus cavernosum of ApoE^−/− mice, which increased the NO‐dependent response in cavernosal strips.ConclusionThese evidences indicate that arginase hyperactivity is associated with ED induced by hypercholesterolemia, suggesting that this enzyme is a potential target for treating ED. Fraga‐Silva RA, Costa‐Fraga FP, Faye Y, Sturny M, Santos RAS, da Silva RF, and Stergiopulos N. An increased arginase activity is associated with corpus cavernosum impairment induced by hypercholesterolemia. J Sex Med 2014;11:1173–1181.     

Urethral Corpus Spongiosum Amyloidosis Presenting with Urethrorrhagia During Erection

IntroductionUrethral amyloidosis is a rare, probably inflammatory condition usually presenting with hematuria and obstructive urinary symptoms, thus mimicking urethral malignancy. After histological confirmation of the diagnosis, treatment can be expectant or symptomatic.AimTo report an unusual cause of urethrorrhagia occurring only during erection in an otherwise healthy man.MethodsA 30-year-old man presented with a 5-month history of urethrorrhagia occurring only during erection, and with a painless palpable nodule in his penile urethra clearly visible on urethral US and magnetic resonance imaging, but not on urethroscopy.ResultsThe patient underwent wide surgical excision of the urethral nodule and grafting of the urethral defect with a pedicled preputial flap. Histological examination revealed isolated amyloid of urethral corpus spongiosum.ConclusionsIsolated urethrorrhagia during erection and without urinary symptoms can be the presenting sign of urethral amyloidosis involving corpus spongiosum rather than the urethral lumen; in such cases, surgical exploration, wide urethral excision and grafting are mandatory. Cormio L, Sanguedolce F, Pentimone S, Perrone A, Annese P, Turri FP, Bufo P, and Carrieri G. Urethral corpus spongiosum amyloidosis presenting with urethrorrhagia during erection. J Sex Med 2009;6:2915–2917.     

Crural tunica albuginea autograft for corporoplasty: an experimental animal study of hemodynamic, histopathological, and molecular effects in the long term

IntroductionCorrection of penile deformity caused by Peyronie's disease by a variety of grafts varies in success. A long-term follow-up shows a significant number of graft scarring and erectile dysfunction. The clinical success of autologous crural tunica albuginea graft (TAG) has not resulted in wide application.AimTo identify in healthy baboons the limitations and merits of autologous crural TAG over 1 year in a way difficult to pursue in humans.MethodsUnder general anesthesia, eight sexually active adult baboons underwent pharmacological cavernosometry (CM) and cavernosography. TAG from crus was implanted in the distal penile shaft. After 6 months, six animals were reevaluated and two were sacrificed, and the penises were excised. After 1 year, the remaining six animals were evaluated and sacrificed. The TAG and underlying corpus cavernosum (CC) were examined histologically and by Western blot analysis for nitric oxide synthase (NOS), neuronal (nNOS), endothelial (eNOS) and inducible (iNOS) isoforms, and transforming growth factor-β₁ (TGF-β₁).Main Outcome MeasuresSexual activity, CM, cavernosography, histopathology, and Western blot analysis.ResultsAll animals resumed normal sexual activity 1 month postsurgery. Cavernous pressure was comparable before, at 6 months, and 1 year after surgery. A cavernovenous insufficiency developed in four animals at 6 months, and ceased in two at 1 year. Penile angulation (<20°) was seen in three animals at 6 months, and an additional two at 1 year. Histologically, TAG was indistinguishable from the adjacent tunica with no fibrosis. In CC, iNOS and nNOS decreased at 1 year, whereas there was no change in TGF-β₁ levels. In TAG, there was no significant change in TGF-β₁ and eNOS levels, but there was a significant decrease in iNOS at 1 year.ConclusionsAutologous free TAG is associated with normal sexual activity, minimal hemodynamic changes, excellent histological outcome, and no rise in iNOS or TGF-β₁. However, cavernovenous insufficiency, mild penile angulation, and decreased nNOS persisted at 1 year. Seyam RM, Mokhtar AA, Chishti MA, Ahmed M, Mourad WA, El-Sayed R, and Hanash KA. Crural tunica albuginea autograft for corporoplasty: An experimental animal study of hemodynamic, histopathological, and molecular effects in the long term.     

Age-Related Morphological Changes in Smooth Muscle and Collagen Content in Human Corpus Cavernosum

IntroductionAging process has been related to erectile dysfunction (ED) possibly due to morphological changes in corpus cavernosum among many other causes.AimTo evaluate smooth muscle and collagen content in human corpus cavernosum and to correlate it to age.MethodsCadaveric human cavernosal tissue was collected during the period of 1 year. Morphological analysis of a whole corpus cavernosum was performed in tissue sections stained with Masson's trichromic method to differentiate smooth muscle (red) from collagen (blue) content.Main Outcome MeasuresAnalysis was performed with specialized micrographs image analysis software. Pearson's correlation test was used to establish correlation between corpus cavernosum morphology (smooth muscle and collagen content) and age.ResultsA total sample of 89 tissues from different male cadavers were analyzed. The average age of the sample was 49.2 ± 19.1 years, with a range between 14 and 90 years. There was a statistically significant inverse correlation between age and the percentage of smooth muscle content (P = 0.012), direct correlation between age and percentage of collagen content (P = 0.019), and inverse correlation between age and the ratio of smooth muscle : collagen content (P = 0.007).ConclusionsAge-related morphological changes in terms of smooth muscle and collagen content are observed in human corpus cavernosum as a possible contributing factor to the development of ED. Ferrer JE, Velez JD, and Herrera AM. Age-related morphological changes in smooth muscle and collagen content in human corpus cavernosum.     

The Neuroprotective Effect of Platelet‐rich Plasma on Erectile Function in Bilateral Cavernous Nerve Injury Rat Model

IntroductionNeurogenic erectile dysfunction resulting from cavernous nerve (CN) injury is a major complication caused by radical prostatectomy. The use of platelet‐rich plasma (PRP) on the nerve‐injured site has shown promising results for the nerve regeneration. However, the effects of PRP injection in corpus cavernosum after bilateral CN injury have never been investigated.AimTo assess the neuroprotective effect of PRP injection in corpus cavernosum after bilateral CN injury.MethodsMale Sprague‐Dawley rats were randomly divided into three groups: Group I underwent sham operation, while the remaining two groups underwent bilateral CN crush. Crush injury groups were treated at the time of injury with an application of PRP or normal saline only injection in the corpus cavernosum, respectively. Four weeks later, erectile function (EF) was assessed by CN electrosimulation, and CNs as well as penile tissue were collected for histology.Main Outcome MeasuresIntracavernous pressure (ICP) monitored during electrical stimulation of CNs; myelinated axons number of CNs and dorsal penile nerve; collagen type change, number of apoptotic cells, and mRNA expression of caspase‐3 and transforming growth factor‐β1 (TGF‐β1) in the corpus cavernosum.ResultsFour weeks after surgery, in the vehicle‐only group, the functional evaluation showed a lower mean maximal ICP than that in the sham group (P < 0.05). PRP treatments resulted in significant recovery of EF, as compared with the vehicle‐only group (P < 0.05). Histologically, the PRP‐treated group had a significant preservation of myelinated axons of CNs compared with the vehicle‐only group (P < 0.05) and reduced the apoptotic index. The mRNA expression of TGF‐β1 in the corpus cavernosum tissue was significantly decreased in the PRP group compared with the vehicle‐only group (P < 0.05).ConclusionsPRP injection in the corpus cavernosum increased the number of myelinated axons and facilitated recovery of EF in the bilateral CN injury rat model. Wu C‐C, Wu Y‐N, Ho H‐O, Chen K‐C, Sheu M‐T, and Chiang H‐S. The neuroprotective effect of platelet‐rich plasma on erectile function in bilateral cavernous nerve injury rat model. J Sex Med 2012;9:2838–2848.     

TNF‐α, Erectile Dysfunction,and NADPH Oxidase‐Mediated ROS Generation in Corpus Cavernosum in High‐Fat Diet/Streptozotocin‐Induced Diabetic Rats

IntroductionPatients with diabetes‐associated erectile dysfunction (ED) are characterized by an increase in circulating tumor necrosis factor‐alpha (TNF‐α). However, no study has indicated whether and how TNF‐α plays a role in the pathogenesis of ED associated with diabetes.AimWe examined the effects and potential mechanism of infliximab (INF), a chimeric monoclonal antibody to TNF‐α, on reactive oxygen species (ROS) generation in corpus cavernosum and ED in diabetic rats.MethodsFour groups of male rats were used: age‐matched normal controls; diabetic rats induced by a high‐fat diet (HFD) combined with a single streptozotocin (STZ) injection (35 mg/kg body weight, intraperitoneal [i.p.]); nondiabetic rats receiving INF (5 mg/kg body weight/week, i.p.), and diabetic rats receiving INF. Erectile function was assessed with electrical stimulation of the cavernous nerve after 8 weeks. The blood and penile tissues were harvested for plasma biochemical determinations, serum TNF‐α measurement, penile ROS detection, and molecular assays of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits, endothelial nitric oxide synthase (eNOS), phospho‐eNOS, and neural nitric oxide synthase (nNOS) in the penis.Main Outcome MeasuresThe effect of INF on HFD/STZ‐induced diabetic ED and NADPH oxidase‐mediated ROS generation was studied in diabetic corpus cavernosum.ResultsUntreated diabetic rats displayed significantly decreased erectile parameters, and increased plasma TNF‐α levels, penile ROS production, p47^phox and gp91^phox expression compared with nondiabetic controls. INF neutralized TNF‐α and significantly reduced ED in diabetic rats, in which marked decreases in p47^phox and gp91^phox expression and ROS generation in corpus cavernosum were noted. The ratio of phospho‐eNOS to eNOS and expression of nNOS in the penis were significantly increased in INF‐treated vs. untreated diabetic rats.ConclusionsIncreased TNF‐α expression associated with diabetes contributes to ED by promoting NAPDH oxidase‐mediated ROS generation in corpus cavernosum. INF protects against diabetic ED by neutralizing TNF‐α. Long T, Liu G, Wang Y, Chen Y, Zhang Y, and Qin D. TNF‐α, erectile dysfunction, and NADPH oxidase‐mediated ROS generation in corpus cavernosum in high‐fat diet/streptozotocin‐induced diabetic rats. J Sex Med 2012;9:1818–1831.     

Voltage‐dependent Ca2+ Currents Contribute to Spontaneous Ca2+ Waves in Rabbit Corpus Cavernosum Myocytes

IntroductionCorpus cavernosum myocytes generate spontaneous tone that contributes to penile detumescence. It is essential to elucidate how tone is generated to fully understand the processes involved in erection. Tissue experiments have shown that blockers of voltage‐dependent Ca²⁺ channels (VDCCs) reduce tone. However, there is also a widespread belief that these channels are poorly expressed in this tissue. Furthermore, it is unclear how VDCC would interact with recently described intracellular Ca²⁺ waves, which initiate contractions.Aims(i) To directly examine VDCC currents in freshly isolated corpus cavernosum myocytes; and (ii) to study the relationship between VDCC and intracellular Ca²⁺ waves.Main Outcome MeasuresVDCC and cytosolic Ca²⁺ were measured using patch clamp and confocal microscopy.MethodsMale New Zealand white rabbits were euthanized and corpus cavernosum myocytes dispersed enzymatically for patch clamp recording and confocal Ca²⁺ imaging (using fluo‐4AM).ResultsIsolated myocytes developed robust VDCC that could be separated into two components. One activated at ?45 mV, reversed at +40 mV, inactivated with a V^1/2 of ?27 mV and was enhanced by Ba²⁺. This component was blocked with nifedipine, but not Ni²⁺ or mibefradil. The other component inactivated with a V^1/2 of ?87 mV, was unchanged in Ba²⁺, and was blocked by Ni²⁺ or mibefradil, but not nifedipine. Even though Ni²⁺ had no effect on intracellular Ca²⁺ waves, nifedipine blocked them, although localized Ca²⁺ events remained.ConclusionsAt least two VDCC are expressed in rabbit corpus cavernousum myocytes. One may be designated L‐type Ca²⁺ current, whereas the other is a putative T‐type current. The L‐current facilitates conversion of local Ca²⁺ events into global Ca²⁺ waves, whereas the putative T‐current plays little part in this process. These results provide a new basis for understanding the role of L‐type Ca²⁺ current in generating detumescent tone in the corpus cavernosum. McCloskey C, Cagney V, Large R, Hollywood M, Sergeant G, McHale N, and Thornbury K. Voltage‐dependent Ca²⁺ currents contribute to spontaneous Ca²⁺ waves in rabbit corpus cavernosum myocytes.     

Testosterone Deficiency Causes Endothelial Dysfunction via Elevation of Asymmetric Dimethylarginine and Oxidative Stress in Castrated Rats

BackgroundTestosterone is believed to mediate the penile erectile response by producing adequate nitric oxide; therefore, testosterone deficiency results in erectile dysfunction through decreased nitric oxide bioavailability. However, the mechanisms underlying endothelial dysfunction in testosterone deficiency remain unclear.AimTo investigate the mechanism of endothelial dysfunction in a rat model of testosterone deficiency.MethodsRats were distributed into 3 groups: castrated (Cast), castrated and supplemented with testosterone (Cast + T), and sham (Sham). In the Cast + T group, castrated rats were treated daily with subcutaneous testosterone (3 mg/kg daily) for 4 weeks; Sham and Cast rats received only the vehicle.OutcomesErectile function using intracavernosal pressure and mean arterial pressure measurements after electrical stimulation of the cavernous nerve, endothelial function using isometric tension, asymmetric dimethylarginine (ADMA) levels using ultra-performance liquid chromatography and tandem mass spectrometry, and inflammatory biomarker expression were performed 4 weeks after the operation.ResultsIn the Cast group, the ratio of intracavernosal pressure to mean arterial pressure significantly decreased, acetylcholine-induced relaxation was lower, and serum ADMA, oxidative stress, and inflammation biomarker levels were significantly increased (P < .01). Testosterone injection significantly improved each of these parameters (P < .01).Clinical TranslationThe present results provide scientific evidence of the effect of testosterone deficiency on erectile function and the effect of testosterone replacement therapy.Strengths and LimitationsThis study provides evidence of the influence of testosterone deficiency on endothelial function by investigating ADMA and oxidative stress. A major limitation of this study is the lack of a direct link of increased ADMA by oxidative stress to inflammation.ConclusionTestosterone deficiency increased not only ADMA levels but also oxidative stress and inflammation in castrated rats, which can cause damage to the corpus cavernosum, resulting in erectile dysfunction.Kataoka T, Hotta Y, Maeda Y, Kimura K. Testosterone Deficiency Causes Endothelial Dysfunction via Elevation of Asymmetric Dimethylarginine and Oxidative Stress in Castrated Rats. J Sex Med 2017;14:1540–1548.     

Metformin Treatment Improves Erectile Function in an Angiotensin II Model of Erectile Dysfunction

IntroductionIncreased angiotensin II (AngII) levels cause hypertension, which is a major risk factor for erectile dysfunction (ED). Studies have demonstrated that increased AngII levels in penile tissue are associated with ED. A recent study showed that metformin treatment restored nitric oxide synthase (NOS) protein expression in penile tissue in obese rats; however, whether metformin treatment can be beneficial and restore erectile function in a model of ED has not yet been established.AimThe goal of this study was to test the hypothesis that AngII induces ED by means of increased corpus cavernosum contraction, and that metformin treatment will reverse ED in AngII-treated rats.MethodsMale Sprague-Dawley rats were implanted with mini-osmotic pumps containing saline or AngII (70 ng/minute, 28 days). Animals were then treated with metformin or vehicle during the last week of AngII infusion.Main Outcome MeasuresIntracavernosal pressure; corpus cavernosum contraction and relaxation; nNOS protein expression; extracellular signal-regulated kinase (ERK1/2), AMP-activated protein kinase (AMPK), and eNOS protein expression and phosphorylation.ResultsAngII-induced ED was accompanied with an increase in corpus cavernosum contractility, decreased nitrergic relaxation, and increased ERK1/2 phosphorylation. Metformin treatment improved erectile function in the AngII-treated rats by reversing the increased contraction and decreased relaxation. Metformin treatment also resulted in an increase in eNOS phosphorylation at ser1177.ConclusionsMetformin treatment increased eNOS phosphorylation and improved erectile function in AngII hypertensive rats by reestablishing normal cavernosal smooth muscle tone. Labazi H, Wynne BM, Tostes R, and Webb RC. Metformin treatment improves erectile function in an angiotensin II model of erectile dysfunction. J Sex Med 2013;10:2154–2164.     

Effects of Oral Finasteride on Erectile Function in a Rat Model

IntroductionMany clinical studies reported finasteride‐related erectile dysfunction, but to date, few animal experiments have focused on it.AimTo investigate the effects of oral finasteride on erectile function in a rat model.Main Outcome MeasuresErectile responses and morphological changes.MethodsAdult, male Sprague‐Dawley rats were divided into four groups (25/group): (i) control; (ii) castration; (iii) castration with testosterone (T) replacement; and (iv) oral finasteride treatment. Four weeks later, erectile function was measured by the ratio of intracavernosal pressure and mean arterial blood pressure upon electrical stimulation of the cavernous nerve. Serum T and dihydrotestosterone (DHT) and intraprostatic DHT were measured. The weights and histopathological features of the penile corpus cavernosum and prostate were examined.ResultsSerum T and DHT and intraprostatic DHT concentrations, erectile function, and mean weights of the corpus cavernosum and prostate were lowest in group 2. There was no significant difference in the serum T concentration and erectile function between groups 4 and 1. However, the serum and intraprostatic DHT concentrations were significantly lower in group 4 than in group 1 (both P < 0.001). The tissue weights of the corpus cavernosum and prostate were reduced by 25.9% and 92.3% in group 4 compared with group 1 (both P < 0.001). Histopathology revealed a significant atrophy of the prostate in groups 2 and 4. There was a significant decrease in the smooth muscle content in group 2, but not in groups 3 and 4.ConclusionsIn a rat model, finasteride treatment for 4 weeks reduces the weight of the corpus cavernosum but appears not to affect the erectile responses to electrical stimulation of the cavernous nerve. As erection is a complex process involving important signaling in the brain, further studies are necessary to demonstrate the long‐term effects of finasteride on both central and peripheral neural pathways of erection. Zhang M‐G, Wu W, Zhang C‐M, Wang X‐J, Gao P‐J, Lu Y‐L, and Shen Z‐J. Effects of oral finasteride on erectile function in a rat model. J Sex Med 2012;9:1328–1336.     

Role of Adenosine Signaling in Penile Erection and Erectile Disorders

IntroductionPenile erection is a hemodynamic process, which results from increased flow and retention of blood in the penile organ due to the relaxation of smooth muscle cells. Adenosine, a physiological vasorelaxant, has been shown to be a modulator of penile erection.AimTo summarize the research on the role of adenosine signaling in normal penile erection and erectile disorders.Main Outcome MeasuresEvidence in the literature on the association between adenosine signaling and normal and abnormal penile erection, i.e., erectile dysfunction (ED) and priapism.MethodsThe article reviews the literature on the role of endogenous and exogenous adenosine in normal penile erection, as well as in erectile disorders namely, ED and priapism.ResultsAdenosine has been shown to relax corpus cavernosum from various species including human in both in vivo and in vitro studies. Neuromodulatory role of adenosine in corpus cavernosum has also been demonstrated. Impaired adenosine signaling through A_2B receptor causes partial resistance of corpus cavernosum, from men with organic ED, to adenosine-mediated relaxation. Increased level of adenosine has been shown to be a causative factor for priapism.ConclusionOverall, the research reviewed here suggests a general role of exogenous and endogenous adenosine signaling in normal penile erection. From this perspective, it is not surprising that impaired adenosine signaling is associated with ED, and excessive adenosine signaling is associated with priapism. Adenosine signaling represents a potentially important diagnostic and therapeutic target for the treatment of ED and priapism. Phatarpekar PV, Wen J, and Xia Y. Role of adenosine signaling in penile erection and erectile disorders.     

Tilapia Skin for Neovaginoplasty after Sex Reassignment Surgery

Study ObjectiveTo describe a new technique of neovaginoplasty after a female sex reassignment surgery using a tilapia skin as a graft.DesignStepwise demonstration of a new technique with narrated video of a single case report. The patient provided oral and written informed consent. Moreover, this video report is part of a multicenter, Investigational Review Board–approved study.SettingWomen's university hospital in Campinas, Brazil.InterventionsNeovaginoplasty technique using tilapia skin with the following key strategies: (1) corpus cavernosum removal, (2) vagina tunnel creation, (3) mold coating with tilapia skin, (4) mold fixation, and (5) postoperative care. The patient remained with the mold coated with tilapia skin for 5 days; after this time, the mold was removed, and the tissue graft was adhered and incorporated in the new vaginal canal. After 2 months, the tissue resembled a vaginal mucosa, and the vaginal length was 8 cm. The patient has not had intercourse yet.ConclusionWe introduce an alternative for low-morbidity neovaginoplasty based on the experience of plastic surgery in burned grafts. The procedure described offers an alternative option to develop an anatomic neovagina with tissue similar to mucosa tissue by a simple, low-morbidity minimally invasive procedure.     

3D reconstruction and histopathological analyses on murine corporal body

PurposeErectile dysfunction (ED) is one of the increasing diseases with aging society. The basis of ED derived from local penile abnormality is poorly understood because of the complex three‐dimensional (3D) distribution of sinusoids in corpus cavernosum (CC). Understanding the 3D histological structure of penis is thus necessary. Analyses on the status of regulatory signals for such abnormality are also performed.MethodsTo analyze the 3D structure of sinusoid, 3D reconstruction from serial sections of murine CC were performed. Histological analyses between young (2 months old) and aged (14 months old) CC were performed. As for chondrogenic signaling status of aged CC, SOX9 and RBPJK staining was examined.ResultsSinusoids prominently developed in the outer regions of CC adjacent to tunica albuginea. Aged CC samples contained ectopic chondrocytes in such regions. Associating with the appearance of chondrocytes, the expression of SOX9, chondrogenic regulator, was upregulated. The expression of RBPJK, one of the Notch signal regulators, was downregulated in the aged CC.ConclusionsProminent sinusoids distribute in the outer region of CC which may possess important roles for erection. A possibility of ectopic chondrogenesis induced by alteration of SOX9/Notch signaling with aging is indicated.