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Frontiers in Endocrinology 2022To assess the diverse cell populations of human corpus cavernosum in patients with severe erectile dysfunction (ED) at the single-cell level.
PURPOSE
To assess the diverse cell populations of human corpus cavernosum in patients with severe erectile dysfunction (ED) at the single-cell level.
METHODS
Penile tissues collected from three patients were subjected to single-cell RNA sequencing using the BD Rhapsody™ platform. Common bioinformatics tools were used to analyze cellular heterogeneity and gene expression profiles from generated raw data, including the packages Seurat, Monocle, and CellPhoneDB.
RESULTS
Disease-related heterogeneity of cell types was determined in the cavernous tissue such as endothelial cells (ECs), smooth muscle cells, fibroblasts, and immune cells. Reclustering analysis of ECs identified an arteriole ECs subcluster and another one with gene signatures of fibroblasts. The proportion of fibroblasts was higher than the other cell populations and had the most significant cellular heterogeneity, in which a distinct subcluster co-expressed endothelial markers. The transition trajectory of differentiation from smooth muscle cells into fibroblasts was depicted using the pseudotime analysis, suggesting that the expansion of corpus cavernosum is possibly compromised as a result of fibrosis. Cell-cell communications among ECs, smooth muscle cells, fibroblasts, and macrophages were robust, which indicated that inflammation may also have a crucial role in the development of ED.
CONCLUSIONS
Our study has demonstrated a comprehensive single-cell atlas of cellular components in human corpus cavernosum of ED, providing in-depth insights into the pathogenesis. Future research is warranted to explore disease-specific alterations for individualized treatment of ED.
Topics: Endothelial Cells; Erectile Dysfunction; Humans; Male; Penile Erection; Penis; Sequence Analysis, RNA
PubMed: 35518933
DOI: 10.3389/fendo.2022.874915 -
Asian Journal of Andrology 2019Although elevated prolactin levels have been shown to inhibit penile erection, the relationship between prolactin and erection of the penile tip or base has not been...
Although elevated prolactin levels have been shown to inhibit penile erection, the relationship between prolactin and erection of the penile tip or base has not been extensively researched. We therefore investigated the prolactin's effects on erection of the penile tip and base, with a cross-sectional study of 135 patients with erectile dysfunction, based on scores of ≤21 on the International Index of Erectile Function-5. All patients were tested for nocturnal penile tumescence, blood pressure, serum glucose, total cholesterol, triglyceride, high-density lipoprotein, low-density lipoprotein, luteinizing hormone, follicle-stimulating hormone, prolactin, estradiol, testosterone, and progesterone. Univariate and multivariate analyses were used to assess the associations between prolactin levels and erection at the penile tip and base. We found no obvious relationship between erection time at penile tip and prolactin levels, but observed a negative correlation between base erection time and prolactin level (hazard ratio: -2.68; 95% confidence interval [CI]: -5.13--0.22). With increasing prolactin concentration, multivariate analysis showed obvious reduction in base erection time among patients with normal Rigiscan results (hazard ratio: -3.10; 95% CI: -7.96-1.77; P < 0.05). Our data indicate that prolactin inhibits penile erection, particularly at the penile base. In addition, when the effective erection time of the penile base lasts longer than 10 min, prolactin has a more obvious inhibitory effect on penile base erection.
Topics: Adult; Cross-Sectional Studies; Erectile Dysfunction; Humans; Male; Penile Erection; Prolactin; Time Factors
PubMed: 31044754
DOI: 10.4103/aja.aja_22_19 -
Scientific Reports Jun 2015Pericytes are known to play critical roles in vascular development and homeostasis. However, the distribution of cavernous pericytes and their roles in penile erection...
Pericytes are known to play critical roles in vascular development and homeostasis. However, the distribution of cavernous pericytes and their roles in penile erection is unclear. Herein we report that the pericytes are abundantly distributed in microvessels of the subtunical area and dorsal nerve bundle of mice, followed by dorsal vein and cavernous sinusoids. We further confirmed the presence of pericytes in human corpus cavernosum tissue and successfully isolated pericytes from mouse penis. Cavernous pericyte contents from diabetic mice and tube formation of cultured pericytes in high glucose condition were greatly reduced compared with those in normal conditions. Suppression of pericyte function with anti-PDGFR-β blocking antibody deteriorated erectile function and tube formation in vivo and in vitro diabetic condition. In contrast, enhanced pericyte function with HGF protein restored cavernous pericyte content in diabetic mice, and significantly decreased cavernous permeability in diabetic mice and in pericytes-endothelial cell co-culture system, which induced significant recovery of erectile function. Overall, these findings showed the presence and distribution of pericytes in the penis of normal or pathologic condition and documented their role in the regulation of cavernous permeability and penile erection, which ultimately explore novel therapeutics of erectile dysfunction targeting pericyte function.
Topics: Animals; Antibodies, Monoclonal; Biomarkers; Cell Separation; Coculture Techniques; Diabetes Mellitus, Experimental; Disease Models, Animal; Endothelial Cells; Erectile Dysfunction; Hepatocyte Growth Factor; Humans; Male; Mice; Penile Erection; Penis; Pericytes; Permeability; Receptor, Platelet-Derived Growth Factor beta
PubMed: 26044953
DOI: 10.1038/srep10891 -
Sexual Medicine Reviews Jan 2018Botulinum toxin type A (BoNT-A) has been used to treat several striated and smooth muscle disorders. During the past year, human and animal studies conducted in Egypt... (Review)
Review
INTRODUCTION
Botulinum toxin type A (BoNT-A) has been used to treat several striated and smooth muscle disorders. During the past year, human and animal studies conducted in Egypt and Canada by two different groups of investigators have suggested a possible role for the intracavernosal injection of BoNT-A in the treatment of erectile dysfunction (ED).
AIM
To discuss BoNT-A and its current medical uses, the rationale for its new potential use in the treatment of ED, and the available evidence and concerns.
METHODS
A literature search was conducted. This review was based on the available studies presented at the European Society for Sexual Medicine, Sexual Medicine Society of North America, and International Society for Sexual Medicine meetings in 2016 by the two groups.
MAIN OUTCOME MEASURES
Sinusoidal diameter; penile color Doppler study; Erection Hardness Score; Sexual Health Inventory for Men questionnaire; and Sexual Encounter Profile questions 2 and 3.
RESULTS
Two human studies conducted by the authors and two animal studies (one from the authors' group and one from Canada) were reviewed. These seemed to suggest generally favorable outcomes with the use of BoNT-A in the treatment of ED.
CONCLUSION
BoNT-A could be a potential therapy for ED. In addition to the findings of the three pilot studies, larger multicenter trials need to be conducted to further explore the true therapeutic efficacy and clinical safety of BoNT-A in the treatment of ED. Ghanem H, Raheem AA, AbdelRahman IFS, et al. Botulinum Neurotoxin and Its Potential Role in the Treatment of Erectile Dysfunction. Sex Med Rev 2018;6:135-142.
Topics: Botulinum Toxins, Type A; Erectile Dysfunction; Evidence-Based Medicine; Humans; Male; Neuromuscular Agents; Penile Erection; Quality of Life; Treatment Outcome
PubMed: 28843941
DOI: 10.1016/j.sxmr.2017.07.008 -
Asian Journal of Andrology Jan 2013Priapism is a rare condition that involves persistent penile erection for greater than 4 h. Distinct variants exist, each with unique characteristics. Ischemic priapism... (Review)
Review
Priapism is a rare condition that involves persistent penile erection for greater than 4 h. Distinct variants exist, each with unique characteristics. Ischemic priapism is a painful medical emergency that may occur as a result of veno-occlusion leading to hypoxia and tissue death. Recurrent bouts of ischemic priapism, or stuttering priapism, require treatment for individual attacks as well as long-term prevention. Non-ischemic priapism is associated with trauma and may be managed conservatively. Recent advances into the pathophysiology of priapism have allowed the development of treatment algorithms that specifically target the mechanisms involved. In this review, we outline the basics of smooth muscle contraction and describe how derangement of these pathways results in priapism. A pathophysiological approach to the treatment of priapism is proposed with duration-based algorithms presented to assist in management.
Topics: Algorithms; Disease Management; Humans; Ischemia; Male; Muscle Contraction; Muscle, Smooth; Penile Erection; Penis; Priapism
PubMed: 23202699
DOI: 10.1038/aja.2012.83 -
Current Topics in Medicinal Chemistry 2007Penile erection is a complex physiologic event resulting from the interactions of the nervous system on a highly specialized vascular organ. Activation of central...
Penile erection is a complex physiologic event resulting from the interactions of the nervous system on a highly specialized vascular organ. Activation of central nervous system melanocortinergic (MC) receptors with either endogenous or synthetic melanotropic ligands may initiate and/or facilitate spontaneous penile erection. While the CNS contains principally the MC3 and MC4 receptor subtypes, there is conflicting data as to which receptor mediates erection. Although the MC4R is emerging as the principle effector of MC induced erection, the role of the MC3R is poorly understood. Manipulation of each receptor subtype with newly synthesized receptor specific agonists and antagonists, as well as knockout mice, has elucidated their individual contributions. Novel data from our laboratories suggests that antagonism of forebrain MC3R may enhance melanocortin-induced erections. Furthermore, melanocortin agents may interact with better-studied systems such as oxytocinergic pathways at the hypothalamic, brainstem or spinal level. Current therapies for erectile dysfunction target end organ vascular tissue. Manipulation of MC receptors may provide an alternative, centrally mediated therapeutic approach for erectile and other sexual dysfunctions. The non-specific "superpotent" MC agonist, PT-141, which is the carboxylate derivative of MT-II, has reached phase II human trials. Through their centrally mediated activity, melanocortin agonists have potential to treat erectile dysfunction as well as possible applications to the unmet medical needs of decreased sexual motivation and loss of libido.
Topics: Animals; Erectile Dysfunction; Humans; Male; Melanocortins; Models, Biological; Penile Erection; Peptides; Receptors, Melanocortin
PubMed: 17584130
DOI: No ID Found -
International Journal of Impotence... Sep 2022Men with Stuttering Priapism (SP) and sleep-related painful erections (SRPE) experience bothersome nocturnal painful erections resulting in poor sleep. The aim of this...
Men with Stuttering Priapism (SP) and sleep-related painful erections (SRPE) experience bothersome nocturnal painful erections resulting in poor sleep. The aim of this study is to observe common features and differences between men with SP and SRPE based on polysomnography, nocturnal penile tumescence (NPT), and penile doppler ultrasound (PDU). This is a prospective cohort study of 20 participants divided into two groups (Group 1 = SP [n = 12]; Group 2 = SRPE [n = 8]) with bothersome painful nocturnal erections. All participants were referred to the sleep disorder clinic to be assessed and consented for overnight polysomnography with simultaneous NPT recording and to complete validated sleep, sexual dysfunction and health-related quality of life questionnaires. Unstimulated PDU was also performed. Abnormal Polysomnographic findings (reduced sleep efficiency, total sleep time, and awake after sleep onset) were identified in both groups suggesting poor sleep. Men with SP had significantly longer erections (60.0 vs 18.5; p = 0.002) and took longer to detumesce once awake (25.7 vs 5.4 min; p = 0.001) than men with SRPE. They also had significantly higher peak systolic and end diastolic velocities on unstimulated PDU with an abnormal low resistance waveform identified. No sleep pathology was identified in men with SP. This implies a local (penile) etiology in men with SP. Men with SRPE had a normal resting PDU and abnormal sleep architecture with REM awakenings and significantly more Periodic limb movements (p = 0.04) than men with SP suggesting a central (sleep-related) cause in men with SRPE. Sexual dysfunction and poor HR-QoL was identified on validated questionnaires in both groups. SP and SRPE are rare entities that share similar symptoms (painful nocturnal erections and poor sleep) but dissimilar features of nocturnal erection onset, duration and resolution with different polysomnographic features which may allude to a different pathophysiology.
Topics: Humans; Male; Pain; Penile Erection; Priapism; Prospective Studies; Quality of Life; REM Sleep Parasomnias; Stuttering; Ultrasonography, Doppler
PubMed: 34389802
DOI: 10.1038/s41443-021-00462-3 -
The Journal of Urology Feb 1995Previous studies have shown that intracavernosal blood flow increases during penile erection, but little is known about intracavernosal hemodynamics. Using a previously...
Previous studies have shown that intracavernosal blood flow increases during penile erection, but little is known about intracavernosal hemodynamics. Using a previously developed canine model of erection, we measured intracavernosal blood flow and oxygen tension at 2 sites within the corpus cavernosum: directly beneath the tunica albuginea and deep within the cavernous tissue. We chose to measure oxygen tension as an indicator of arterial blood flow. Penile erection was induced by pelvic nerve stimulation as well as by injection of papaverine and phentolamine. In the flaccid penis, blood flow measured directly under the tunica albuginea was significantly higher than deep intracavernosal blood flow. Subtunical oxygen tension in the flaccid penis was consistent with a largely arterial circulation. These observations provide physiological evidence of an important subtunical circulation that carries most of the intracavernosal blood flow when the penis is flaccid. With pelvic nerve stimulation, deep intracavernosal blood flow increased significantly followed by an increase in oxygen tension. Oxygen tension deep within the corpus cavernosum increased during penile erection from a level consistent with venous blood to a level consistent with arterial blood. Injection of papaverine and phentolamine caused a significant increase in intracavernosal pressure and a significant decrease in subtunical blood flow but did not cause statistically significant change in intracavernosal blood flow or oxygen tension. In contrast to nerve-induced erection, pharmacologically induced erection appears to depend more on intracavernosal shunting of blood than on increased total arterial blood flow to the penis. Hypogastric nerve stimulation during established erection caused detumescence by contracting cavernosal smooth muscle, reducing deep cavernosal blood flow and reestablishing blood flow through the subtunical space. Our observations suggest that the subtunical space contains an important circulation that may play a role in the hemodynamics of the flaccid, as well as the erect, penis.
Topics: Animals; Arteries; Blood Gas Analysis; Dogs; Electric Stimulation; Hemodynamics; Male; Oxygen; Papaverine; Penile Erection; Penis; Phentolamine; Regional Blood Flow
PubMed: 7815637
DOI: 10.1097/00005392-199502000-00075 -
The Journal of Sexual Medicine Jun 2019Although sex aids have been used in clinical practice for ages, the scientific literature assessing their application in men with sexual dysfunction is limited. (Review)
Review
BACKGROUND
Although sex aids have been used in clinical practice for ages, the scientific literature assessing their application in men with sexual dysfunction is limited.
AIM
To summarize medical literature regarding scientific uses of the most common sex aids in men with sexual dysfunction and assess their clinical applicability.
METHODS
An extensive literature review was performed with regard to the use of sex aids in sexual medicine. Our search included journal articles, books, and guidelines in different databases: Embase, PubMed, and Cochrane. The key words were "sex aids," "sex toys," "pornography," "lubricants," "constriction bands," "dildos," "vibrators," "vacuum devices," "external penile devices," and "sex swings" were searched. Date of last search was December 4, 2018.
MAIN OUTCOME MEASURES
We assessed the utility of sex aids in men with sexual dysfunction and formulated recommendations for clinicians.
RESULTS
Various sex aids are available for men with sexual dysfunction. We present a comprehensive review of the most common sex aids currently available: pornography, lubricants, constriction bands, dildos, vibrators, vacuum devices, external erectile support devices, and aids to positioning. We discuss their indications, outcomes, precautions, and complications.
CLINICAL IMPLICATIONS
This review is intended to provide sexual medicine practitioners and academics an overview of sex aids for men with sexual dysfunction for use in both clinical practice and research.
STRENGTHS & LIMITATIONS
This is a compilation of scientific data for a topic that has broad application in sexual medicine and yet has been poorly addressed in the scientific literature. Because of the lack of sufficient data and the heterogeneous nature of different sex aids, a systematic review could not be performed.
CONCLUSION
Having a comprehensive understanding of the sexual dynamics of individuals and couples combined with the appropriate integration of sex aids may have a positive effect in the treatment of male sexual dysfunctions. Miranda EP, Taniguchi H, Cao DL, et al. Application of Sex Aids in Men With Sexual Dysfunction: A Review. J Sex Med 2019;16:767-780.
Topics: Erectile Dysfunction; Erotica; Humans; Lubricants; Male; Penile Erection; Penis; Photic Stimulation; Play and Playthings; Sexual Behavior; Sexual Dysfunctions, Psychological; Vacuum
PubMed: 31029536
DOI: 10.1016/j.jsxm.2019.03.265 -
Journal of Oncology Practice Apr 2016Cancer can cause sexual adverse effects by direct and indirect pathways. It can involve sexual organs, indirectly affect body image, or cause fatigue or depression with... (Review)
Review
Cancer can cause sexual adverse effects by direct and indirect pathways. It can involve sexual organs, indirectly affect body image, or cause fatigue or depression with subsequent effects on libido. Erectile dysfunction (ED), the inability to obtain or maintain an erection firm enough for sexual intercourse, can also result from adverse effects of cancer treatment, such as fatigue, pain, or anxiety about therapy. In addition, depressed feelings about having cancer can affect sexuality, causing a range of signs and symptoms that can lead to ED. Chemotherapy, hormone therapy, surgery, and radiation can all cause sexual adverse effects. Additional factors that play a role include patient age and degree of ED before starting cancer treatment. In this article, we discuss how chemotherapy, hormone therapy, surgery, and radiation affect erectile function as well as possible treatment options for ED.
Topics: Combined Modality Therapy; Disease Management; Erectile Dysfunction; Humans; Male; Neoplasms; Penile Erection; Treatment Outcome
PubMed: 27072383
DOI: 10.1200/JOP.2016.010678