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Nature Communications Jul 2022The corpus cavernosum is the most important structure for penile erection, and its dysfunction causes many physiological and psychological problems. However, its...
The corpus cavernosum is the most important structure for penile erection, and its dysfunction causes many physiological and psychological problems. However, its cellular heterogeneity and signalling networks at the molecular level are poorly understood because of limited access to samples. Here, we profile 64,993 human cavernosal single-cell transcriptomes from three males with normal erection and five organic erectile dysfunction patients. Cell communication analysis reveals that cavernosal fibroblasts are central to the paracrine signalling network and regulate microenvironmental homeostasis. Combining with immunohistochemical staining, we reveal the cellular heterogeneity and describe a detailed spatial distribution map for each fibroblast, smooth muscle and endothelial subcluster in the corpus cavernosum. Furthermore, comparative analysis and related functional experiments identify candidate regulatory signalling pathways in the pathological process. Our study provides an insight into the human corpus cavernosum microenvironment and a reference for potential erectile dysfunction therapies.
Topics: Erectile Dysfunction; Humans; Male; Muscle, Smooth; Penile Erection; Penis; Transcriptome
PubMed: 35879305
DOI: 10.1038/s41467-022-31950-9 -
Annals of Medicine and Surgery (2012) Dec 2022Congenital megalourethra is a urogenital anomaly characterized by a cystic dilatation and elongation of the penile urethra resulting from the absence and hypoplasia of...
BACKGROUND
Congenital megalourethra is a urogenital anomaly characterized by a cystic dilatation and elongation of the penile urethra resulting from the absence and hypoplasia of the corpus spongiosum and corpus cavernosum, or anterior urethral valve. There are two clinical types: scaphoid and fusiform. Generally, the etiology is unknown, but it is thought to be a defect in mesodermal development. Fewer than 100 cases have been reported in the literature, and the exact incidence is unclear. In most cases, the surgical procedure is challenging and requires extensive reconstructive and/or replacement surgery.
CASE PRESENTATION
We present a 6-month-old boy suffering from a cystic dilatation of the penile urethra along with urine dribbling during micturition since birth. The patient was diagnosed with the scaphoid type of megalourethra and was operated on using reduction urethroplasty. On the 21st post-operative day, we removed the Foley catheter and followed the patient on two occasions (the 45th post-operative day and the 6th post-operative month) with excellent results.
CONCLUSION
The anagement of megalourethra depends on the clinical type. Meticulous surgical technique, the use of fine suture materials with careful handling, and fixation of the vascularized flap are the main principles of an acceptable result. Observation of erectile function and fertility require long-term follow-up.
PubMed: 36582879
DOI: 10.1016/j.amsu.2022.104926 -
Stem Cell Research & Therapy Sep 2022Erectile dysfunction (ED), as one of the most prevalent consequences in male diabetic patients, has a serious impact on men's physical and mental health, and the...
BACKGROUND
Erectile dysfunction (ED), as one of the most prevalent consequences in male diabetic patients, has a serious impact on men's physical and mental health, and the treatment effect of diabetic mellitus erectile dysfunction (DMED) is often worse. Therefore, the development of a novel therapeutic approach is urgent. As stem cells with high differentiation potential, human umbilical cord mesenchymal stem cells (HUCMSCs) have been widely used in the treatment of diseases in other systems, and are expected to be a promising strategy for the treatment of DMED. In this study, we investigated the role of HUCMSCs in managing erectile function in rat models of type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) and compared the effects of two different injection methods.
METHODS
T1DM and T2DM ED rats were given labelled HUCMSCs by corpus cavernosum injection and tail vein injection, respectively. ICP and MAP were monitored simultaneously by electrical stimulation four weeks after injection to indicate the erectile function of rats. To track the development and colonisation capabilities of stem cells, we performed EdU assay with penile tissue. The histological changes of the penis were observed by hematoxylin-eosin staining, and Masson's trichrome staining was conducted to evaluate the smooth muscle content and the degree of fibrosis in the rat penis. Then, we employed specific kits to measure the level of NO, cGMP, MDA, SOD and Fe in penis. Electron transmission microscopy was implemented to observe morphology of mitochondria. Besides, western blot and immunofluorescence staining were performed to demonstrate the expression of ferroptosis-related genes.
RESULTS
We found that HUCMSCs improved erectile function in T1DM and T2DM ED rats, with no difference in efficacy between corpus cavernosum injection and tail vein injection. The EdU assay revealed that only a tiny percentage of HUCMSCs colonised the corpus cavernosum, while smooth muscle in the penis expanded and collagen decreased following HUCMSC injection. Moreover, the levels of oxidative stress in the penis of the rats given HUCMSCs were dramatically reduced, as was the tissue iron content. HUCMSCs normalised mitochondrial morphology within corpus cavernosum smooth muscle cells (CCSMCs), which were characteristically altered by high glucose. Furthermore, the expression of ferroptosis inhibitory genes SLC7A11 and GPX4 was obviously elevated in CCSMCs after stem cell management, but the abundances of ACSL4, LPCAT3 and ALOX15 showed the polar opposite tendency.
CONCLUSIONS
HUCMSCs can effectively and safely alleviate erectile dysfunction in T1DM and T2DM ED rats, while restoring erectile function by attenuating diabetes-induced ferroptosis in CCSMCs. Additionally, this study provides significant evidence for the development of HUCMSCs as a viable therapeutic strategy for DMED.
Topics: Animals; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Erectile Dysfunction; Ferroptosis; Humans; Male; Mesenchymal Stem Cells; Rats; Rats, Sprague-Dawley; Umbilical Cord
PubMed: 36064453
DOI: 10.1186/s13287-022-03147-w -
Cells Jan 2022Lithium has been a mainstay of therapy for patients with bipolar disorders for several decades. However, it may exert a variety of adverse effects that can affect... (Review)
Review
Lithium has been a mainstay of therapy for patients with bipolar disorders for several decades. However, it may exert a variety of adverse effects that can affect patients' compliance. Sexual and erectile dysfunction has been reported in several studies by patients who take lithium as monotherapy or combined with other psychotherapeutic agents. The exact mechanisms underlying such side effects of lithium are not completely understood. It seems that both central and peripheral mechanisms are involved in the lithium-related sexual dysfunction. Here, we had an overview of the epidemiology of lithium-related sexual and erectile dysfunction in previous clinical studies as well as possible pathologic pathways that could be involved in this adverse effect of lithium based on the previous preclinical studies. Understanding such mechanisms could potentially open a new avenue for therapies that can overcome lithium-related sexual dysfunction and improve patients' adherence to the medication intake.
Topics: Animals; Disease Models, Animal; Erectile Dysfunction; Humans; Lithium; Male; Models, Biological
PubMed: 35011733
DOI: 10.3390/cells11010171 -
Clinical Practice and Cases in... Aug 2020We describe a case of spontaneous partial segmental thrombosis of the corpus cavernosum (PSTCC).
CASE PRESENTATION
We describe a case of spontaneous partial segmental thrombosis of the corpus cavernosum (PSTCC).
DISCUSSION
PSTCC is a rare condition in which thrombus formation occurs in the corpus cavernosum. This condition is managed in conjunction with a urologist, and management typically includes anticoagulation and pain control.
PubMed: 32926730
DOI: 10.5811/cpcem.2020.7.47903 -
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 -
Reproductive Medicine and Biology 2023The corpus cavernosum (CC) containing sinusoids plays fundamental roles for erection. Analysis of pathological changes in the erectile system is studied by recent... (Review)
Review
BACKGROUND
The corpus cavernosum (CC) containing sinusoids plays fundamental roles for erection. Analysis of pathological changes in the erectile system is studied by recent experimental systems. Various in vitro models utilizing genital mesenchymal-derived cells and explant culture systems are summarized.
METHODS
3D reconstruction of section images of murine CC was created. Ectopic chondrogenesis in aged mouse CC was shown by a gene expression study revealing the prominent expression of Sox9. Various experimental strategies utilizing mesenchyme-derived primary cells and tissue explants are introduced.
MAIN FINDINGS
Possible roles of Sox9 in chondrogenesis and its regulation by several signals are suggested. The unique character of genital mesenchyme is shown by various analyses of external genitalia (ExG) derived cells and explant cultures. Such strategies are also applied to the analysis of erectile contraction/relaxation responses to many signals and aging process.
CONCLUSION
Erectile dysfunction (ED) is one of the essential topics for the modern aged society. More comprehensive studies are necessary to reveal the nature of the erectile system by combining multiple cell culture strategies.
PubMed: 37663955
DOI: 10.1002/rmb2.12539 -
The World Journal of Men's Health Apr 2024Autophagy is a conservative lysosome-dependent material catabolic pathway, and exists in all eukaryotic cells. Autophagy controls cell quality and survival by... (Review)
Review
Autophagy is a conservative lysosome-dependent material catabolic pathway, and exists in all eukaryotic cells. Autophagy controls cell quality and survival by eliminating intracellular dysfunction substances, and plays an important role in various pathophysiology processes. Erectile dysfunction (ED) is a common male disease. It is resulted from a variety of causes and pathologies, such as diabetes, hypertension, hyperlipidemia, aging, spinal cord injury, or cavernous nerve injury caused by radical prostatectomy, and others. In the past decade, autophagy has begun to be investigated in ED. Subsequently, an increasing number of studies have revealed the regulation of autophagy contributes to the recovery of ED, and which is mainly involved in improving endothelial function, smooth muscle cell apoptosis, penile fibrosis, and corpus cavernosum nerve injury. Therefore, in this review, we aim to summarize the possible role of autophagy in ED from a cellular perspective, and we look forward to providing a new idea for the pathogenesis investigation and clinical treatment of ED in the future.
PubMed: 38606869
DOI: 10.5534/wjmh.230145 -
Andrology Jul 2022To describe the association between partial thrombosis of the corpus cavernosum, partial priapism, and hard flaccid syndrome. (Review)
Review
AIM
To describe the association between partial thrombosis of the corpus cavernosum, partial priapism, and hard flaccid syndrome.
METHODS
A scoping review was performed according to the recommendations of the Joanna Briggs Institute. Moreover, we performed a search strategy using the MEDLINE, EMBASE, and CENTRAL databases. We included the available information, evaluating the conditions of partial thrombosis of the corpus cavernosum, partial priapism, and hard flaccid syndrome, and their molecular and physiological mechanisms and clinical presentation.
RESULTS
We identified 207 articles and chose eight studies published between 2001 and 2021. The total number of patients was 34, and their mean age was 28.2 years. Moreover, in 84% of the studies, the pathophysiology of the events was related to microtrauma or prolonged perineal compression. Additionally, 94.2% of the patients had some degree of erectile dysfunction. In addition, out of all patients, 94% underwent magnetic resonance imaging (MRI). However, patients with hard flaccid syndrome did not show relevant findings in these studies. Conversely, MRI showed asymmetry in the proximal corpora cavernosa, thrombosed corpus cavernosum segments, and mainly cavernous fibrous septum in patients with partial cavernous thrombosis and partial priapism.
CONCLUSION
Partial thrombosis of the corpus cavernosum, partial priapism, and hard flaccid syndrome occurred more frequently in young patients, possibly related to microtraumas that generate cavernous fibrosis and trigger alterations in the erection of the distal portion of the penis. Additionally, they cause proximal hardening of the pelvis, perineal pain, painful ejaculations, and cavernous asymmetry. Moreover, the imaging characteristics are similar in patients with partial priapism and partial cavernous thrombosis.
Topics: Adult; Humans; Magnetic Resonance Imaging; Male; Pelvic Pain; Penis; Priapism; Thrombosis
PubMed: 35460544
DOI: 10.1111/andr.13190 -
Archivos Espanoles de Urologia Sep 2022Thrombosis of the corpus cavernosum is a rare disease of unknown cause that usually affects young men. We present the case of a 25-year-old man with an unilateral,...
Thrombosis of the corpus cavernosum is a rare disease of unknown cause that usually affects young men. We present the case of a 25-year-old man with an unilateral, painful perineal mass and ultrasound scan compatible with this entity. The magnetic resonance and tomography computarised scan images corroborate the diagnosis. Anticoagulants were prescribed which solved the clinical picture.
Topics: Adult; Anticoagulants; Humans; Male; Penile Diseases; Penis; Thrombosis; Ultrasonography
PubMed: 36214151
DOI: 10.56434/j.arch.esp.urol.20227507.97