Selcuk Yucel

Induction of hypospadias in a murine model by maternal exposure to synthetic estrogens.

We tested the hypothesis that maternal exposure to synthetic estrogen can cause hypospadias in male offspring and defined the morphological changes in the disrupted urethral seam. Timed pregnant C57/6 mice were exposed to synthetic estrogens. The genital tubercles were examined for the presence of hypospadias using histology, three-dimensional computer reconstruction, and plastic cast injection molds of the urethra. Microscopic serial analysis confirmed the presence of hypospadias, which occurred in approximately 50% of the synthetic-estrogen-treated male fetuses. No effect was seen in the female embryos. Plastic cast injection showed that affected males had a shorter total urethral length and loss of male anatomic features such as the prostatic utricle. Exposure to synthetic estrogens during pregnancy affects the normal development of the urethra in the mouse. We conclude that endocrine disrupters play an important role in genital tubercle anomalies.

Neuroanatomy of the male urethra and perineum

To describe the topography of the perineal nerves from their pudendal origin to their course into the male genitalia, with specific attention on the course of the perineal nerve along the ventral penis, including branches into bulbospongiosus muscle and corpus spongiosum.

The effect of oestrogen and testosterone on the urethral seam of the developing male mouse genital tubercle

To describe the effects of exogenous oestrogens and androgens on urethral formation in the mouse, as the development of the mouse and human urethra have significant similarities, and understanding normal male urethral development may help to identify the causes of abnormal development, e.g. hypospadias.

Anatomical Studies of the Fibroblast Growth Factor-10 Mutant, Sonic Hedge Hog Mutant and Androgen Receptor Mutant Mouse Genital Tubercle

OBJECTIVESnCongenital genital abnormalities have a diverse spectrum from hypospadias to cloacal anomalies. The molecular events in the normal and abnormal development of the genital tubercle (GT) are still obscure. Genetically engineered mice with specific gene deletions that affect genital anatomy are a useful tool to better understand the etiology of genital abnormalities. In this study, we compared the genital tubercle anatomy of the androgen receptor (AR) deficient, fibroblastic growth factor (FGF)-10 deficient and Sonic HedgeHog (Shh) deficient mutant male mice to that of the wild type male and female mouse.nnnMATERIALS AND METHODSnThe lower pelvis of the androgen receptor deficient, FGF-10 deficient, Shh deficient mutant male and wild type male and female mouse at different gestational days (E13-21) and post natal ages (1 day-1 week) were studied. GTs were imaged, serially sectioned and stained immunohistochemically with antibodies raised against E-Cadherin, Cytokeratin 7, 10 and 14. Serial sections of the GTs were selected and three-dimensional computerized images were created to better elucidate the anatomy.nnnRESULTSnAR deficient mutant male mouse revealed a distinctive GT anatomy, different from both sexes. The corporal bodies and glans remained hypoplastic whereas the urethral spongiosa was more developed than the wild type female counterpart. This finding is consistent with the AR mutant mouse being a unique morphologic phenotype distinct from the normal male and female. FGF-10 deficient mutant male mouse revealed normal corporal bodies with failure of the urethral plate to fuse ventrally consistent with hypospadias. The Shh deficient mutant mouse demonstrated complete agenesis of GT outgrowth and a persistent cloaca.nnnCONCLUSIONnAnimal models bred by gene knockout technology or natural occurring mutants contribute to the basic understanding of normal and abnormal GT development. The anatomy of the these three mutant mice confirms the importance of the androgen receptor, FGF-10 and Shh in genital development.

The neuroanatomy of the human scrotum: surgical ramifications

The developmental neuroanotomy of the human scrotum may not have been evaluated up to now, but the authors from San Francisco report here on an outstanding study in foetuses of this important area of interest. They have helped to define clearly the neuroanotomy of this region, which will be useful in planning surgery to the scrotum and penis in children.

Anatomical Studies of the Mouse Genital Tubercle

BACKGROUNDnTo study the etiology of hypospadias, we propose the use of a mouse model, the embryonic mouse genital tubercle. In this study, we define the development of the mouse genital tubercle with special emphasis on urethral formation demonstrating anatomical similarities to human development.nnnMATERIALS AND METHODSnSerial sections of genital tubercles from embryonic male and female mice ages 14 to 21 days gestation from timed pregnant animals, newborn and adult mice were immunohistochemical stained with antibodies to E-cadherin, cytokeratins 7, 10, and 14. Patency of the urethral was assessed by india ink injection via the bladder. Urethral lumen morphology was determined by the creation of plastic resin cast. Surface morphology of the genital tubercle was defined by scanning electron microscopy.nnnRESULTSnIndia Ink injection into the bladder showed that the urethral lumen was patent from 14 days gestation. Plastic resin casts revealed that the male urethra was characterized by a S shaped curve, the presence of the bulbar urethral gland and a longer length than age matched females. The ontogeny of the genital tubercle development revealed two epithelial edges that subsequently touched and fused into the completed urethra. During development cytokeratin immunohistochemical staining demonstrated that the epithelial cells of the urethral lumen are of bladder origin and the surface cells of skin origin.nnnCONCLUSIONnThe functional and developmental anatomy of the mouse genital tubercle provides a useful model to study normal and abnormal human urethral development.

Endoscopic Vesicoureteral Reflux Correction in Transplanted Kidneys: Does Injection Technique Matter?

AIM AND BACKGROUNDnPosttransplant vesicoureteral reflux (VUR) is a common urologic complication after renal transplantation, although its management is controversial. The treatment of choice is open surgical revision ureteral reimplantation with significant morbidity. Recently, endoscopic correction by using nonanimal dextranomer/hyaluronic acid copolymer (NA Dx/HA) injection has been reported to be effective in the treatment of VUR of transplanted kidneys. Herein, we present our 3-year endoscopic correction results in transplanted kidneys where we used two different injection techniques, subureteral and intraureteral.nnnMATERIALS AND METHODSnWe retrospectively reviewed all patients who underwent endoscopic VUR correction of posttransplant VUR by NA Dx/HA injection between July 2005 and March 2009. We excluded patients with underlying urologic abnormalities.nnnRESULTSnA total of 26 patients (14 women and 12 men) with a mean age of 32.2 years (range: 15–55) were studied. The VUR was also graded as nondilating reflux in 10 (grade I–II) and dilating reflux in 16 (grade III–IV). Seventeen ureters (5 nondilating and 12 dilating VUR) were injected NA Dx/HA intraureterally, and 9 ureters (5 nondilating and 4 dilating VUR) were injected NA Dx/HA subureterally. Overall success rate was 53.8% (14 out of 26). Intraureteral injection technique was successful in nine cases (52.9%), and subureteral injection technique was successful in five cases (55.5%). In nondilating VUR, injection corrected 90% (9 out of 10) of posttransplant patients, whereas in dilating VUR group injection corrected only 31.25% (5 out of 16). We found no statistical significance of injection technique on the success rate.nnnCONCLUSIONSnEndoscopic correction by using NA Dx/HA with any injection technique seems to be a plausible alternative to correction of refluxing posttransplant ureters, particularly in nondilating VUR.

Long-term effects of pediatric extracorporeal shockwave lithotripsy on renal function.

Introduction Extracorporeal shock wave lithotripsy (ESWL) is a well-known and successful treatment modality. In addition, it can be used in premature infants. ESWL is used to treat kidney and ureter stones in children. However, although it is a preferred noninvasive treatment in that setting, there is debate about its long-term effects on growing kidneys in children. Objectives To investigate the long-term effects of pediatric ESWL on renal function in light of updated literature. Methods PubMed and Medline were searched for studies on ESWL in a pediatric population with keywords including efficacy, child, kidney calculi, ureter calculi, lithotripsy, injury, vascular trauma, and shock waves. The research was limited to the English literature during a period from 1980 to 2014. In total, 3,000 articles were evaluated, but only 151 papers were considered. Only the manuscripts directly related to the reviewed subjects were included in the current study. Results However, the acute effects of ESWL in kidney are well-described. Although there are limited studies on the long-term effects of ESWL in children, there is a widespread opinion that ESWL is not affecting renal functions in the long-term. Conclusion ESWL is a safe, effective, and noninvasive treatment option in children. Although ESWL can cause some acute effects in the kidney, there is no long-term effect on the growing kidneys of children.

A neuroanatomical comparison of humans and spotted hyena, a natural animal model for common urogenital sinus: clinical reflections on feminizing genitoplasty.

PURPOSEnSurgical treatment of the common urogenital sinus phallus has been one of the most challenging areas in pediatric urology. To better understand the neuroanatomy of the common urogenital sinus phallus, we evaluated an animal model naturally having this condition, the spotted hyena, Crocuta crocuta. We compared the neuroanatomy of male and female humans and spotted hyenas using anatomical, immunohistochemical and 3D reconstruction techniques. We also examined the implications of the pattern of clitoral innervation for the unique challenges faced by female spotted hyenas, the only extant species of mammal that mates and gives birth through the clitoris.nnnMATERIALS AND METHODSnThree adult male and 3 female spotted hyenas were studied. With the animals under anesthesia gross anatomical examination was performed before and after artificial erection. Histological analysis was performed on one 95-day fetal male and female spotted hyena specimens, and on 18 human male and female fetal external genitalia specimens using antibodies raised against the neuronal marker S-100. Three-dimensional computer reconstruction using serial sections allowed analysis of the neuroanatomy of the penis, clitoris and common urogenital sinus of the fetal spotted hyena and human.nnnRESULTSnCompared to other mammals, the clitoris and penis of spotted hyenas were remarkably similar in size and configuration in the flaccid and erect states. Male and female hyenas had a single opening on the tip of the glans penis/clitoris. The basic anatomical structures of the corporeal bodies in both sexes of humans and spotted hyenas were similar. As in humans, the dorsal nerve distribution was unique in being devoid of nerves at the 12 oclock position in the penis and clitoris of the spotted hyena. Dorsal nerves of the penis/clitoris in humans and male spotted hyenas tracked along both sides of the corporeal body to the corpus spongiosum at the 5 and 7 oclock positions. The dorsal nerves penetrated the corporeal body and distally the glans in the hyena. In female hyenas the dorsal nerves fanned out laterally on the clitoral body. Glans morphology was different in appearance in both sexes, being wide and blunt in the female and tapered in the male.nnnCONCLUSIONSnThe neuroanatomy of the male and female external genitalia in the spotted hyena, Crocuta crocuta, although grossly similar, has distinct anatomical and functional characteristics. The clitoris of the spotted hyena is a classic example of a natural animal model of a common urogenital sinus. The neuroanatomical characteristics of the spotted hyena may be a useful model to simulate the anatomy of common urogenital sinus anomaly in humans.

Current Medical Diagnosis and Management of Vesicoureteral Reflux in Children

Vesico-ureteral reflux (VUR) is presented in approximately %1 of children and is associated with an increased risk of pyelonephritis and renal scarring. Despite its prevalence and morbidity, many aspects of VUR diagnosis and treatment are controversial. We objectively assessed the published data; the data base for many current diagnoses and treatment patterns of VUR is limited. Recent studies have focused on developed determination of VUR-related renal morbidity, improved stratification tools that children would benefit most from which VUR treatment option, and improved reporting of the long-term outcomes of VUR treatments in children who are at risk for VUR. In this review, the advances in the diagnosis and treatment of VUR will be accompanied by the current guidelines.