The effect of zinc sulfate on penile corpus spongiosum after hypospadias repair in rats: A stereological study.

Hypospadias repair involves correcting urethra defects and improving the wound healing process. Zinc has been well accepted as an effective agent in wound healing. This study aimed to investigate the effect of zinc on corpus spongiosum after experimental hypospadias in rats. The animals were divided into three groups. The control group rats underwent general anesthesia, but did not receive any surgeries and treatments. The second and third groups underwent surgeries and respectively received Distilled Water (DW, 2 ml) and zinc sulfate solution (2 ml, containing 4 mg zinc sulfate) by gavages twice a day for 14 days. Stereological methods were used to quantify the corpus spongiosum tissue. The volumes of corpus spongiosum, spongy tissue, urethral lumens, urethral epithelium, and collagen bundles and the number of fibroblasts were respectively amplified by 28%, 40%, 36%, 48%, 40%, and 29% in the surgery + zinc sulfate group in comparison to the surgery + DW group (p < 0.02). It can be concluded that consumption of 4 mg/day zinc sulfate for 14 days could improve the healing of hypospadias through increasing the population of fibroblasts, producing collagen bundles, and building a wider lumen and more epithelized urethra.

Testicular disorder of sexual development with cryptorchidism, penile hypoplasia and hypospadias in a giraffe (Giraffa camelopardalis giraffa).

Disorders of sexual development (DSD) in wild mammals are rarely described. A male South African giraffe (Giraffa camelopardalis giraffa) was identified with bilateral cryptorchidism. The testes were intra-abdominal, smaller and less ovoid than in normal male giraffes. The right testis was situated more cranially than the left and connected to a longer deferent duct with normal ampullae. One distended vesicular gland filled with mucoid material was identified. A short penis, situated in the perineal area, was directed caudally and presented hypospadias. Histologically, testicular hypoplasia was present; the epididymis tubules contained no spermatozoa and the deferent duct and vesicular gland were inflamed. The blood testosterone concentration was 16.27 nmol/L and oestrone sulphate concentration was 0.03 ng/mL. The aetiology of the abnormalities is unknown.

Clinical, cytogenetic and molecular genetic characterization of a tandem fusion translocation in a male Holstein cattle with congenital hypospadias and a ventricular septal defect.

Hypospadias, disorder of sex development (DSD), is a sporadic congenital abnormality of the genital region in male ruminants, which is characterized by a non-fused urethra during fetal development. Detailed clinical examination classified the hypospadias phenotype of a male Holstein calf studied here as the perineal type. In combined use of cytogenetic analysis and whole genome sequencing, a non-mosaic, pseudo-monosomy 59, XY + tan(18;27) was detected. This chromosomal aberration had its origin in a tandem fusion translocation of the bovine autosomes (BTA) 18 and 27 with an accompanying loss of genomic sequences mainly in the distal end of BTA 18 and the proximal end of BTA 27. The resulting phenotype included hypospadias, growth retardation and ventricular septal defect.

Cloacal malformation in a 5-month-old male dog.

A case of a developmental cloacal anomaly is described in a 5-month-old male puppy. The animal had a unique combination of anomalies: confluence of the urethra and rectum into a common tract with a single perineal opening, atresia ani, and 3 genital anomalies, namely, a perineal hypospadias, penile hypoplasia with ventroflexural curvature, and a scrotal cleft. Surgical correction was successful, with fecal continence maintained and no urinary tract infections occurring during long-term follow-up.

Malformation cloacale chez un chiot mâle âgé de cinq mois. Un cas de développement cloacal anormal est décrit chez un chiot mâle âgé de cinq mois. L'animal avait une combinaison unique d'anomalies : une confluence de l'urètre et du rectum dans un tractus commun avec une ouverture périnéale unique, une atrésie de l'anus, et trois anomalies génitales, à savoir, un hypospadias périnéal, une hypoplasie pénienne avec courbure ventroflexurale, et une fissure scrotale. La correction chirurgicale fut une réussite, avec la continence fécale maintenue et aucune infection du tractus urinaire se produisant durant le suivi à long terme.(Traduit par Dr Serge Messier).

Polymorphisms of MAMLD1, SRD5A2, and AR Candidate Genes in Seven Dogs (78,XY; SRY-Positive) Affected by Hypospadias or Cryptorchidism.

Knowledge of the molecular background of disorders of sex development (DSD) in dogs with normal sets of XY chromosomes (XY DSD) is very scarce. However, extensive studies have been carried out in humans, showing that polymorphisms and mutations of numerous genes, including SRY, MAMLD1, SRD5A2, and AR, are associated with or responsible for XY DSD. In this study, we analyzed the entire coding sequence of these genes in 7 dogs (78,XY) with ambiguous external genitalia (hypospadias, cryptorchidism, bifid scrotum, or rudimentary penis). The most common disorder was hypospadias (6 cases), followed by cryptorchidism (4 cases). The co-occurrence of both abnormalities was observed in 3 dogs. Polymorphisms were found in MAMLD1 (3 SNPs), SRD5A2 (5 SNPs), and AR (2 STRs and 1 SNP), while SRY was monomorphic. However, the distribution of the polymorphic variants in the DSD dogs and 11 control XY dogs did not differ significantly. Our study suggests that an association between the polymorphisms of the studied candidate genes and hypospadias or cryptorchidism is unlikely in dogs. We thus support the recent suggestion that hypospadias is not rare in this species, and moreover, we show that co-occurrence of hypospadias and cryptorchidism can be quite frequent.

Single stage urethroplasty for perineal hypospadias in a horse: A case report.

INTRODUCTION: Within the veterinary world, data regarding the surgical management of hypospadias is lacking. Reports within equines have documented resective phallectomy procedures rather than urethral reconstruction. This case report documents the first ever urethroplasty for an equine hypospadias, performed by a consultant paediatric surgeon. The urethroplasty was achieved by applying the same surgical principles mastered from paediatric urology to a horse. The indication for surgery was contact dermatitis of the hind-leg, which impaired the thoroughbred foal's racing potential. OPERATION: A single stage urethroplasty was performed, during which the wide urethral plate was tubularised in two layers and the urethral meatus was successfully relocated distally to open upon the glans. The urethroplasty was covered with dartos fascia and the penile shaft skin and prepuce were reconstructed. Post-operatively, urine flowed cranially and the contact dermatitis resolved. Minor superficial wound dehiscence was observed which was managed conservatively and self-resolved. Follow-up at 3 years confirmed the horse continues to void from the re-sited meatus without complication and went on to have an illustrious career within horseracing. CONCLUSION: We have documented the first reconstructive urethroplasty for hypospadias within a horse, achieved by adopting the surgical techniques normally implemented within paediatric urology with good functionality.

[Perineal hypospadia in a red Holstein-calf. A case report]. / Perineale Hypospadie bei einem rotbunten Deutsche-Holstein-Kalb. Ein Fallbericht.

Hypospadia is a congenital deformation of the urethra. Several surgical correction methods have been described, but there are also cases when an operation is not necessarily required. In this report, the case of a bull calf which did not need an invasive therapy will be presented.

Testicular disorder of sex development in four cats with a male karyotype (38,XY; SRY-positive).

The molecular background of disorders of sex development (DSD) in cats is poorly recognized. In this study we present cytogenetic, molecular and histological analyses of four cats subjected for the analysis due to ambiguous external genitalia. Three cases, with rudimentary penises and an abnormal position of the urethral orifice, represented different types of hypospadias. The fourth case had a normal penis, a blind vulva and spermatogenetically active testes. Histological studies showed structures typical of testes, but spermatogenic activity was observed in two cats only. All the cats had a normal male chromosome complement (38,XY) and the Y-chromosome linked genes (SRY and ZFY) were also detected. Fluorescent in situ hybridization (FISH), with the use of the feline BAC probe harboring the SRY gene, excluded the possibility of chromosome translocation of the Y chromosome fragment carrying the SRY gene onto another chromosome. Sequencing of four candidate genes (SRY--sex determining region Y; AR--androgen receptor; SRD5A2--steroid-5-alfa reductase 2 and MAMLD1--mastermind-like domain containing (1) revealed one SNP in the SRY gene, one common polymorphism in exon 1 of the AR gene (tandem repeat of a tri-nucleotide motif--CAG), six polymorphisms (5 SNPs and 1 indel) in the SRD5A2 gene and one SNP in the MAMLD1 gene. Molecular studies of the candidate genes showed no association with the identified polymorphisms, thus molecular background of the studied DSD phenotypes remains unknown.

Hipospadia perineal em um cão: relato de caso / Perineal hypospadias in a dog: case report

A hipospadia é uma anomalia congênita da genitália externa, na qual a uretra peniana termina ventral e caudalmente à sua abertura normal. Pode ser classificada, com base na localização da abertura uretral, como glandular, peniana, escrotal, perineal e anal. O objetivo deste trabalho é relatar um caso raro de hipospadia perineal, em que são abordados seus aspectos clínicos e terapêuticos, em um cão macho, sem raça definida, com seis meses de idade. Um canino com histórico de suspeita de hermafroditismo e presença de um orifício, logo abaixo do ânus, pelo qual urinava foi atendido no Hospital de Clínicas Veterinárias da Universidade Federal do Rio Grande do Sul (UFRGS). Durante o exame físico, foi observado o meato uretral localizado ventralmente ao ânus, além de alterações no prepúcio, pênis e escroto. Foram realizados exames de triagem, tais como: hemograma completo, urinálise, ecografia abdominal e uretrocistografia. O cão foi encaminhado para a cirurgia, quando foi submetido à amputação peniana e prepucial total e também à orquiectomia. O canino recebeu antibioticoterapia, analgésicos, anti-inflamatório e limpezas diárias dos pontos e da região perineal e apresentou excelente recuperação pós-operatória. Após 30 dias da cirurgia, o paciente retornou ao hospital, e foi verificada completa cicatrização da ferida cirúrgica, sem sinais de infecção urinária e inflamação ou assaduras na região perineal. A hipospadia perineal é um caso raro de anomalia uretral congênita, ainda pouco documentada em medicina veterinária. O procedimento cirúrgico realizado demonstrou ser importante, uma vez que removeu toda a genitália externa defeituosa, onde, futuramente, poderiam desenvolver-se infecções e/ou inflamações. Com isso, minimizou as complicações dessa doença e melhorou a qualidade de vida do paciente...

Hypospadias is a congenital anomaly of the external genitalia, where the penile urethra finishes its normal opening ventrally and caudally. It can be classified based on the location of the urethral opening as glandular, penile, scrotal, perineal and anal. The aim of this work was report an uncommon case of perineal hypospadias, working on the clinical and therapeutic aspects in a six-month-old male dog of undefined race. A dog with a history of suspected hermaphroditism and presenting a hole below the anus by which it urinated, was rescued at the Veterinary Teaching Hospital of the Federal University of Rio Grande do Sul (UFRGS). During the physical exam, it was observed that the urethral meatus was situated ventrally to the anus. Foreskin, penis and scrotum alterations were also seen on the dog. Screening exams such as complete blood count, urinalysis, abdominal ultrasound and cystourethrography were done. The dog went straight to surgery, where it had total penile and total preputial amputation and also orchiectomy. The canine showed excellent postoperative recovery, receiving antibiotic therapy, analgesics, anti-inflammatories and daily cleaning on stitches and the perineal region. Thirty days after surgery the patient went back to the Hospital presenting a complete healing of the surgical wound, without reporting signs of urinary infection and inflammation or rashes on the perineal region. The perineal hypospadias is a rare case of urethral congenital anomaly, still not well documented by veterinary medicine. The surgical procedure done demonstrated to be important, since there was the removal of all of the defective external genitalia where, in the future, inflammation and infection could develop, decreasing the complications of this disease and improving this patient's quality of life...

Use of a preputial circumferential mucosal flap for hypospadias management in a Boston terrier.

An eight-week-old male Boston terrier presented for penile desiccation and urine pooling in the prepuce due to congenital hypospadias. An advancement flap was created from the dorsal mucosa of the incompletely formed prepuce and sutured circumferentially to construct a longer distal preputial mucosa. V- to Y-plasty of the ventral abdominal skin was utilised to create the preputial skin overlying the mucosal flap. Urethrostomy and partial penile amputation were also performed. Following surgery, the clinical signs of penile desiccation and preputial urine pooling resolved and acceptable cosmetic appearance was achieved. This technique may be considered for glandular or penile hypospadias or following resection of the ventral aspect of the distal prepuce when inadequate tissue is present for a simple two-layer closure of the preputial mucosa and skin.

Disorders of sexual development in the domestic horse, Equus caballus.

Abnormalities of sexual development causing infertility in horses have been investigated since the early 1970's. Conventional cytogenetic analysis by karyotyping has been the primary tool used to investigate these horses. Abnormalities have a broad range, from a phenotypically normal mare with gonadal dysgenesis to a horse with ambiguous external genitalia and internal male and female organs. Cytogenetic analysis can determine genetic sex but cannot identify mutations or deletions of genes involved in the sex determination pathway. Molecular technologies have been developed to confirm cytogenetic results and to aid in identifying the genetic causes of abnormal sex determination in horses. In this paper, we review the historical development of methods used to understand abnormal sexual development in the horse as well as summarize cases reported over the last 40-50 years.

Gonadal and sex differentiation abnormalities of dogs and cats.

The molecular steps in normal sexual development were largely discovered by studying patients and animal models with disorders of sexual development (DSD). Although several types of DSD have been reported in the cat and dog, which are often strikingly similar to human DSD, these have been infrequently utilized to contribute to our knowledge of mammalian sexual development. Canine and feline cases of DSD with sufficient evidence to be considered as potential models are summarized in this report. The consensus DSD terminology, and reference to previous terminology, is used to foster adoption of a common nomenclature that will facilitate communication and collaboration between veterinarians, physicians, and researchers. To efficiently utilize these unique resources as molecular tools continue to improve, it will be helpful to deposit samples from valuable cases into repositories where they are available to contribute to our understanding of sexual development, and thus improve human and animal health.

A survey of congenital reproductive abnormalities in rams in abattoirs in South west England.

Congenital abnormalities of the reproductive tract of male sheep were surveyed at three abattoirs in the south west of England during the period June 2000-January 2004. A total of 7307 rams were examined [6521 lambs (prepubescent) and hoggets (aged from their first autumn after birth until first shorn) and 786 adult rams mature rams that had been exposed to ewes]. A total of 156 congenital lesions were detected, 87 of which occurred in lambs. Testicular hypoplasia was the most common lesion occurring in 69 lambs as well as eight hoggets ('microtestes' were recognized in nine other animals in which the testis was disproportionately smaller than the epididymis). The second most common lesion found was notched scrotum occurring in 34 animals (27 young rams and seven adults). Some cases of notched scrotum were accompanied by hypospadias which was seen in a total of seven lambs and eight hoggets. Other lesions, detected in five or less animals (less than approximately 0.05% of the animals examined), included cryptorchidism and various abnormalities of the epididymis (segmental aplasia of the epididymis, blind efferent ducts and epididymal cyst) and congenital scrotal hernia. The overall prevalence of congenital lesions of 2.21% emphasizes the importance of undertaking breeding soundness examinations of young rams before they are put with the flock.

Hypospadias in a male (78,XY; SRY-positive) dog and sex reversal female (78,XX; SRY-negative) dogs: clinical, histological and genetic studies.

Hypospadias is rarely reported in dogs. In this study we pre-sent 2 novel cases of this disorder of sexual development and, in addition, a case of hereditary sex reversal in a female with an enlarged clitoris. The first case was a male Moscow watchdog with a normal karyotype (78,XY) and the presence of the SRY gene. In this dog, perineal hypospadias, bilateral inguinal cryptorchidism and testes were observed. The second case, representing the Cocker spaniel breed, had a small penis with a hypospadic orifice of the urethra, bilateral cryptorchidism, testis and a rudimentary gonad inside an ovarian bursa, a normal female karyotype (78,XX) and a lack of the SRY gene. This animal was classified as a compound sex reversal (78,XX, SRY-negative) with the hypospadias syndrome. The third case was a Cocker spaniel female with an enlarged clitoris and internally located ovotestes. Cytogenetic and molecular analyses revealed a normal female karyotype (78,XX) and a lack of the SRY gene, while histology of the gonads showed an ovotesticular structure. This case was classified as a typical hereditary sex reversal syndrome (78,XX, SRY-negative). Molecular studies were focused on coding sequences of the SRY gene (case 1) and 2 candidates for monogenic hypospadias, namely MAMLD1 (mastermind-like domain containing 1) and SRD5A2 (steroid-5-alpha-reductase, alpha polypeptide 2). Sequencing of the entire SRY gene, including 5'- and 3'-flanking regions, did not reveal any mutation. The entire coding sequence of MAMLD1 and SRD5A2 was analyzed in all the intersexes, as well as in 4 phenotypically normal control dogs (3 females and 1 male). In MAMLD1 2 SNPs, including 1 missense substitution in exon 1 (c.128A>G, Asp43Ser), were identified, whereas in SRD5A2 7 polymorphisms, including 1 missense SNP (c.358G>A, Ala120Thr), were found. None of the identified polymorphisms cosegregated with the intersexual phenotype, thus, we cannot confirm that hypospadias may be associated with polymorphism in the coding sequence of the studied genes.

Hypospadias in a Friesian gelding.

OBJECTIVE: To report clinical signs and management of hypospadias in a horse. STUDY DESIGN: Clinical report. ANIMAL: A 6-year-old, Friesian gelding. METHODS: Partial phallectomy was performed to resolve contact dermatitis of the pelvic limbs and abnormal behavior during urination. Subsequent urethral meatal stenosis was treated by revision. RESULTS: Hypospadias and chordee caused altered direction of urine flow, contact dermatitis of the pelvic limbs, and abnormal behavior. Partial phallectomy and subsequent revision after meatal stenosis resolved urine direction, flow and abnormal behavior. CONCLUSIONS: Abnormalities of the urinary tract associated with hypospadias can result in urine-induced, contact dermatitis and distress during urination, but these complications can be resolved by partial phallectomy.