Contrasting mechanisms of penile urethral formation in mouse and human.

This paper addresses the developmental mechanisms of formation of the mouse and human penile urethra and the possibility that two disparate mechanisms are at play. It has been suggested that the entire penile urethra of the mouse forms via direct canalization of the endodermal urethral plate. While this mechanism surely accounts for development of the proximal portion of the mouse penile urethra, we suggest that the distal portion of the mouse penile urethra forms via a series of epithelial fusion events. Through review of the recent literature in combination with new data, it is unlikely that the entire mouse urethra is formed from the endodermal urethral plate due in part to the fact that from E14 onward the urethral plate is not present in the distal aspect of the genital tubercle. Formation of the distal portion of the mouse urethra receives substantial contribution from the preputial swellings that form the preputial-urethral groove and subsequently the preputial-urethral canal, the later of which is subdivided by a fusion event to form the distal portion of the mouse penile urethra. Examination of human penile development also reveals comparable dual morphogenetic mechanisms. However, in the case of human, direct canalization of the urethral plate occurs in the glans, while fusion events are involved in formation of the urethra within the penile shaft, a pattern exactly opposite to that of the mouse. The highest incidence of hypospadias in humans occurs at the junction of these two different developmental mechanisms. The relevance of the mouse as a model of human hypospadias is discussed

Controversy about embryogenesis and organisation of human female urethra: A review

Objective: To assess current knowledge on development and associated structures.Data sources: Current scientific publications in the pubmed data base on the development of human female urethra were reviewed. The embryology of human female urethra and its associated structures is presented.Study selection: The following search words: urethra development, female urethra development, and male urethra development were used.Data extraction: The first 100 publications from urethra development search and thereafter 100 publications excluding those in the first search were reviewed to determine whether they described development of female urethra.Data synthesis: There are limited studies describing the formation of female urethra. Unlike male urethra, female urethra does not undergo masculinisation meaning there is no formation of clitoral urethra. Like the male urethra, there are female urethra associated glands whose presence and functions remain speculative. Female urethra associated structures including Skene’s glands also referred to as female prostate, corpus spongiosum of female urethra and what has been described as the G-Spot may all be congenital malformations considering that they are not uniformly present.Conclusions: Female urethra development differs from that of males though there are some similarities. Studies to elucidate the development of female urethra are needed to clarify some of the misconceptions and to provide embryological explanation of gross and histological features of female urethra

Perineal urethrostomy: surgical and functional evaluation of two techniques

Introduction. PU is an option to manage complex and/or recurrent urethral strictures and is necessary after urethrectomy and/or penectomy. PU is generally assumed to be the last option before abandoning the urethral outlet. Methods. Between 2001 and 2013, 51 patients underwent PU. Mean age (+/- standard deviation) was 60 +/- 15 years. Only 13 patients (25.5%) did not undergo previous urethral interventions. PU was performed according to the Johanson (n = 35) or Blandy (n = 16) technique and these 2 groups were compared for surgical failure, maximum urinary flow (Q(max)), urinary symptoms, and quality of life (according to the International Prostate Symptom Score). Results. Both groups were similar for patient's and stricture characteristics. Only follow-up duration was significantly longer after Johanson PU (47.9 months versus 11.1 months; P = 0.003). For the entire cohort, 11 patients (21.6%) were considered a failure (9 or 25.7% for Johanson group and 2 or 12.5% for Blandy group; P = 0.248). There was a significant improvement of Q(max) in both groups. Quality of life after PU was comparable in both groups. Conclusions. PU is associated with a 21.6% recurrence rate and the patient should be informed about this risk

Mechanisms of pelvic floor muscle function and the effect on the urethra during a cough

Background: Current measurement tools have difficulty identifying the automaticphysiologic processes maintaining continence, and many questions still remainabout pelvic floor muscle (PFM) function during automatic events.Objective: To perform a feasibility study to characterise the displacement, velocity,and acceleration of the PFM and the urethra during a cough.Design, setting, and participants: A volunteer convenience sample of 23 continentwomen and 9 women with stress urinary incontinence (SUI) from the generalcommunity of San Francisco Bay Area was studied.Measurements: Methods included perineal ultrasound imaging, motion trackingof the urogenital structures, and digital vaginal examination. Statistical analysisused one-tailed unpaired student t tests, and Welch’s correction was applied whenvariances were unequal.Results and limitations: The cough reflex activated the PFM of continent women tocompress the urogenital structures towards the pubic symphysis, which wasabsent in women with SUI. The maximum accelerations that acted on the PFMduring a cough were generally more similar than the velocities and displacements.The urethras of women with SUI were exposed to uncontrolled transverse accelerationand were displaced more than twice as far ( p = 0.0002), with almost twicethe velocity ( p = 0.0015) of the urethras of continent women. Caution regardingthe generalisability of this study is warranted due to the small number of women inthe SUI group and the significant difference in parity between groups.Conclusions: During a cough, normal PFM function produces timely compressionof the pelvic floor and additional external support to the urethra, reducing displacement,velocity, and acceleration. In women with SUI, who have weakerurethral attachments, this shortening contraction does not occur; consequently,the urethras of women with SUI move further and faster for a longer duratio

Clitoral development in the mouse and human.

The goal of this report is (a) to provide the first detailed description of mouse clitoral development, and (b) to compare mouse and human clitoral development. For this purpose, external genitalia of female mice were examined by wholemount microscopy, histology and immunohistochemistry from 14 days of gestation to 10 days postnatal. Human clitoral development was examined by these techniques as well as by scanning electron microscopy and optical projection tomography from 8 to 19 weeks of gestation. The adult mouse clitoris is an internal organ defined by a U-shaped clitoral lamina whose development is associated with the prenatal medial and distal growth of the female preputial swellings along the sides of the genital tubercle to form the circumferential preputial lamina. Regression of the ventral aspect of the preputial lamina leads to formation of the U-shaped clitoral lamina recognized as early as 17 days of gestation. While the adult U-shaped mouse clitoral lamina is closely associated with the vagina, and it appears to be completely non-responsive to estrogen as opposed to the highly estrogen-responsive vaginal epithelium. The prominent perineal appendage in adult females is prepuce, formed via fusion of the embryonic preputial swellings and is not the clitoris. The human clitoris is in many respects a smaller anatomic version of the human penis having all of the external and internal elements except the urethra. The human clitoris (like the human penis) is derived from the genital tubercle with the clitoral glans projecting into the vaginal vestibule. Adult morphology and developmental processes are virtually non-comparable in the mouse and human clitoris

Flutamide-induced hypospadias in rats: A critical assessment.

This paper provides the first detailed description of flutamide-induced hypospadias in the rat based upon wholemount, histologic, three-dimensional reconstruction, scanning electron microscopic, and immunocytochemical analysis. The penile malformations elicited by this potent anti-androgen include a substantial proximal shift in the urethral meatus that clearly conforms to the definition of hypospadias based upon specific morphological criteria for this malformation. Through examination of the normal penile development and flutamide-induced abnormal penile development observed in prenatally oil- and flutamide-treated rats, our analysis provides insights into the morphogenetic mechanism of development of hypospadias. In this regard, a common theme in normal penile development is midline fusion of epithelia followed by removal of the epithelial seam and establishment of midline mesenchymal confluence during development of the penile urethra and prepuce, processes which are impaired as a result of prenatal flutamide treatment. The developmental processes occurring in normal penile development, through comparison with development of female external genitalia and those impaired due to prenatal flutamide treatment, are consistent with critical role of androgen receptors in normal penile development in the rat, and the specific penile abnormalities embodied in flutamide-induced rat hypospadias

Complex epithelial remodeling underlie the fusion event in early fetal development of the human penile urethra.

We recently described a two-step process of urethral plate canalization and urethral fold fusion to form the human penile urethra. Canalization ("opening zipper") opens the solid urethral plate into a groove, and fusion ("closing zipper") closes the urethral groove to form the penile urethra. We hypothesize that failure of canalization and/or fusion during human urethral formation can lead to hypospadias. Herein, we use scanning electron microscopy (SEM) and analysis of transverse serial sections to better characterize development of the human fetal penile urethra as contrasted to the development of the human fetal clitoris. Eighteen 7-13 week human fetal external genitalia specimens were analyzed by SEM, and fifteen additional human fetal specimens were sectioned for histologic analysis. SEM images demonstrate canalization of the urethral/vestibular plate in the developing male and female external genitalia, respectively, followed by proximal to distal fusion of the urethral folds in males only. The fusion process during penile development occurs sequentially in multiple layers and through the interlacing of epidermal "cords". Complex epithelial organization is also noted at the site of active canalization. The demarcation between the epidermis of the shaft and the glans becomes distinct during development, and the epithelial tag at the distal tip of the penile and clitoral glans regresses as development progresses. In summary, SEM analysis of human fetal specimens supports the two-zipper hypothesis of formation of the penile urethra. The opening zipper progresses from proximal to distal along the shaft of the penis and clitoris into the glans in identical fashion in both sexes. The closing zipper mechanism is active only in males and is not a single process but rather a series of layered fusion events, uniquely different from the simple fusion of two epithelial surfaces as occurs in formation of the palate and neural tube

Revision of perineal urethrostomy using a meshed split-thickness skin graft

Perineal urethrostomy is considered to be the last option to restore voiding in complex/recurrent urethral stricture disease. It is also a necessary procedure after penectomy or urethrectomy. Stenosis of the perineal urethrostomy has been reported in up to 30% of cases. There is no consensus on how to treat a stenotic perineal urethrostomy, but, in general, a form of urinary diversion is offered to the patient. We present the case of a young male who underwent perineal urethrostomy after urethrectomy for urethral cancer. The postoperative period was complicated by wound dehiscence with subsequent complete obliteration of the perineal urethrostomy. Revision surgery was performed with reopening of the obliterated urethral stump and coverage of the skin defect between the urethra and the perineal/scrotal skin with a meshed split-thickness skin graft. To date, this patient is voiding well and satisfied with the offered solution