Intra-abdominal Cryptorchidism Research Articles

Mouse Mutants of Relaxin, Insulin-Like 3 Peptide and their Receptors

Recently, mouse mutants of closely related relaxin (Rln1), insulin-like3 (Insl3), and GPCR receptors ( Lgr7 and Lgr8/Great) have been produced using gene targeting approach in ES cells and transgenesis. Analysis of their phenotype allowed an identification of the cognate ligand/receptors interactions, specific target organs, and physiological and developmental processes regulated by Rln and Insl3 signaling. Females deficient for Rln1 or Lgr7 exhibit undeveloped mammary gland nipples and increased parturition time during pregnancy. The Rln1 deficiency results in a buildup of fibrosis in different organs and an accumulation of collagen, concurrent with the known effects of Rln1 on extracellular matrix metabolism. Rln1-/- mice have an age-related progression of lung fibrosis with increasing collagen content and concentration, alveolar congestion, and bronchiole epithelium thickening. Male-specific abnormalities were detected in renal and cardiac function of the older Rln1-deficient animals; additionally, poor development of mutant male reproductive organs has been reported. The Insl3-/- or Lgr8-/- male mice exhibit high intraabdominal cryptorchidism. It is caused by the failure of gubernacular ligament differentiation, a structure mediating transabdominal testis descent during male embryogenesis. Transgenic mice with an overexpression of both hormones have been produced; they were instrumental in defining the specificity of Rln1 and Inls3 signaling. Mutant mice provide the experimental models to study the diverse actions of both hormones in vivo. Keywords: relaxin, insulin-like, lgr, gene targeting, mouse mutations

A stereological study of the effects of experimental inguinal cryptorchidism and subsequent orchiopexy on spermatogenesis in adult monkeys.

Our previous study demonstrated that experimental intra-abdominal cryptorchidism in adult rabbits for 13 weeks resulted in severe spermatogenic arrest: type A spermatogonia was the only germ cell type seen in the seminiferous epithelium and its number per testis was reduced by 84%. Seven weeks following orchiopexy, the type A spermatogonial number returned to the near-normal range in most animals and spermatogenesis partially recovered (Reproduction 2002, 124, 95-105). This study aimed to determine whether inguinal cryptorchidism would produce less-severe damage to spermatogenesis and whether subsequent orchiopexy would better restore spermatogenesis. Five normal adult male rhesus monkeys (Macaca mulatta) underwent bilateral artificial inguinal cryptorchidism. Half a year later, one testis together with the ipsilateral epididymis were removed from each animal and then unilateral orchiopexy was performed on the contralateral side, with the remaining testis and epididymis being removed another half a year later. A contemporary unbiased and efficient stereological tool, the optical disector, was used to estimate numbers of all types of spermatogenic cells in the testis and spermatozoa in the epididymis. Spermatogenic arrest was induced by cryptorchidism at the stage of spermatogonia (n = 1), spermatocytes (n = 2) or early spermatids (n = 1), with the type A spermatogonial numbers per testis being reduced to 14.8-57.2% of the control average; in one of the five cryptorchid animals, however, spermatogenesis remained normal. Subsequent orchiopexy, which was successfully performed on two animals with cryptorchidism-induced spermatogenic arrest, brought on a full or partial recovery of spermatogenesis. In conclusion, inguinal cryptorchidism induces less severe (in comparison with an intra-abdominal one) and variable damage to spermatogenesis, which is restored, at least in part, by subsequent orchiopexy.

Effects of Orchiopexy on Congenitally Cryptorchid Insulin-3 Knockout Mice

Insulin-3 (Insl3) knockout mice exhibit isolated, bilateral, high intra-abdominal cryptorchidism. If left in this position until adulthood, these testes will deteriorate to the Sertoli-cell-only state, leading to infertility in 100%. We examined the effect of orchiopexy in this genetically engineered animal model.A total of 160 testes from 80 male offspring of Insl3 F crosses underwent either no orchiopexy (29 testes), sham surgery (25 testes), 1-stage Fowler-Stephens scrotal orchiopexy (57 testes) or primary orchiopexy into a low abdominal, subcutaneous pouch (49 testes). A group of postoperative mice underwent fertility testing 3 months postoperatively. At 6 to 9 months postoperatively the testes were harvested and histologically analyzed.Testes were atrophic in 100% (25 of 25) of the sham group, 91% (52 of 57) of the Fowler-Stephens orchiopexy group and 33% (16 of 49) of the subcutaneous pouch group (testis weight less than 50 mg.). Fertility testing was done in 30 mice (sham 5, Fowler-Stephens orchiopexy 17 and subcutaneous pouch 8). Infertility was secondary to bilateral testicular atrophy (sham 5 of 5, Fowler-Stephens orchiopexy 13 of 17), spermatogenic maturation arrest (subcutaneous pouch 8 of 8) and ductal obstruction [normal spermatogenesis with epididymis devoid of sperm] (Fowler-Stephens orchiopexy 2 of 17). Fertility with normal spermatogenesis was observed in 2 of 17 Fowler-Stephens orchiopexy mice, both of which were Insl3 knockout mice.Intrascrotal orchiopexy can rescue these congenitally cryptorchid Insl3 knockout testes from their intra-abdominal fate of Sertoli-cell-only and lead to fertility. The results suggest that orchiopexy has a crucial and central role in preservation of spermatogenesis.

Mutations of the GREAT gene cause cryptorchidism.

In humans, failure of testicular descent (cryptorchidism) is one of the most frequent congenital malformations, affecting 1-3% of newborn boys. The clinical consequences of this abnormality are infertility in adulthood and a significantly increased risk of testicular malignancy. Recently, we described a mouse transgene insertional mutation, crsp, causing high intraabdominal cryptorchidism in homozygous males. A candidate gene Great (G-protein-coupled receptor affecting testis descent), was identified within the transgene integration site. Great encodes a seven-transmembrane receptor with a close similarity to the glycoprotein hormone receptors. The Great gene is highly expressed in the gubernaculum, the ligament that controls testicular movement during development, and therefore may be responsible for mediating hormonal signals that affect testicular descent. Here we show that genetic targeting of the Great gene in mice causes infertile bilateral intraabdominal cryptorchidism. The mutant gubernaculae fail to differentiate, indicating that the Great gene controls their development. Mutation screening of the human GREAT gene was performed using DHPLC analysis of the genomic DNA from 60 cryptorchid patients. Nucleotide variations in GREAT cDNA were found in both the patient and the control populations. A unique missense mutation (T222P) in the ectodomain of the GREAT receptor was identified in one of the patients. This mutant receptor fails to respond to ligand stimulation, implicating the GREAT gene in the etiology in some cases of cryptorchidism in humans.

Mutation analysis of the GREAT (G Protein-Coupled receptor affecting testis descent) gene in cryptorchid patients

Objective: We have recently identified a novel gene, Great, which causes infertile bilateral intra-abdominal cryptorchidism in homozygous Great knockout mice. Here, we performed mutation screening of the human GREAT gene using denaturing high-pressure liquid chromatographic (DHPLC) analysis of cryptorchid patients. Relaxin is known to activate the GREAT receptor through the adenosine 3,5-monophosphate (cAMP)-dependent pathway. We used relaxin to analyze the functional properties of the mutant receptor that was identified.

Fertility and histological studies of the contralateral testes in two different intra- and extra-abdominal rat models of unilateral cryptorchidism.

To investigate the effect of location of the testis on both testicular development and fertility in unilateral cryptorchidism. Forty-nine Wistar King A newborn male rats were divided into three groups. In group 1 (15 rats) intra-abdominal unilateral cryptorchidism were created by the intra-abdominal fixation of the testis in the neonatal period. In group 2 (16 rats) extra-abdominal unilateral cryptorchidism was created by extra-abdominal fixation of the gubernaculum in the neonatal period. In group 3, 18 rats underwent a sham operation as controls. At 90 days of age, fertility was then assessed in each rat by housing it with two mature virgin females for 2 weeks. Thereafter, at 115-120 days of age, the rats were killed and their testes removed for histological examination. There was no significant difference in the pregnancy rate between females coupled with rats from any group, but the mean number of offspring was significantly lower in females coupled with rats in group 1 than in group 2. Furthermore, histological examination of both the cryptorchid and contralateral scrotal testes showed more severe changes in the intra-abdominal than the extra-abdominal testes. These results suggest that intra-abdominal cryptorchid testes are significantly more impaired than extra-abdominal cryptorchid testes, and that such impairment might be caused by exposure of the testis to a higher temperature. The more severely impaired undescended testes may thus induce the degeneration of the contralateral scrotal testis and thereby cause subfertility in the intra-abdominal unilateral cryptorchid rat model.

SURGICAL MANAGEMENT OF THE NONPALPABLE TESTIS: THE CHILDREN'S HOSPITAL OF PHILADELPHIA EXPERIENCE

Purpose The management of the nonpalpable testis permits an individualized operative approach. We analyze the results of surgical management of a large series of patients with a nonpalpable testis. Materials and Methods Between January 1986 and June 1994 we treated 1,866 boys with undescended testes. There were 447 testes (24%) that were not palpable at presentation. Intraoperative data on these patients were collected for age at presentation, bilateral testes position, testicular size, associated inguinal anomalies (vas, epididymis and processus vaginalis) and surgical approach. For intra-abdominal testes postoperative results of 2 surgical techniques, the Fowler-Stephens procedure and Koop orchiopexy (retroperitoneal mobilization of spermatic vessels and vas) were compared in 76 patients with at least 18 months of followup. Results Average patient age at presentation was 34 months with 63% presenting before age 48 months. Of the impalpable testes 58% were on the left side, 35% were on the right side and 7% were bilateral. At operation 181 testes (41%) were atrophic or absent, 91 (20%) were intraabdominal with 14 (3.1%) bilateral, 136 (30%) were in the inguinal canal and 39 (9%) were in other locations, including 22 at the pubic tubercle, 2 in the upper scrotum, 13 in the superficial inguinal pouch and 2 in the perineum. Of the intra-abdominal group associated extratesticular malformations were identified in 36 cases (39%). Attachment of the vas deferens to the testis was abnormal in 23 of 64 cases (36%), including 10 that were completely detached and 13 with head or tail attachment only. Of the 91 evaluable cases in the intra-abdominal group 38 (42%) had been treated with the Fowler-Stephens repair (5 in 2 stages), 33 (36%) with inguinal orchiopexy and intraperitoneal dissection without dividing the spermatic vessels, 5 with 2-stage procedures and vessel preservation and 14 (15%) with orchiectomy. One testis was left in situ. The inguinal approach with intraperitoneal extension was successful in defining the testis location or blind-ending vas and vessels in 100% of the cases. A single operation to perform orchiopexy was successful in 92% of the cases. Overall, results were considered excellent or acceptable in 32 of 33 cases (97%) after Koop orchiopexy and 28 of 38 (74%) after the Fowler-Stephens orchiopexy. Conclusions Nonpalpable testes accounted for 24% of the patients presenting with undescended testes. At surgical exploration 39% of impalpable testes were distal to the external inguinal ring, 41% were atrophic or absent and 20% were intra-abdominal. All cases were treated through a standard inguinal incision. These data provide evidence that the inguinal approach to orchiopexy with transperitoneal mobilization of the vas and vessels without transection is highly successful for the intra-abdominal cryptorchid testis and, to date, is the preferred technique for the management of the intra-abdominal undescended testis.

Temporary intraabdominal cryptorchidism in the weanling rat leads to irreversible azoospermia: W.J. Kort, I. Hekking-Weijma, and M. Vermeij. J Surg Res 51:138–142, (August), 1991

Temporary intraabdominal cryptorchidism in the weanling rat leads to irreversible azoospermia: W.J. Kort, I. Hekking-Weijma, and M. Vermeij. J Surg Res 51:138–142, (August), 1991

Temporary intraabdominal cryptorchidism in the weanling rat leads to irreversible azoospermia

To study surgical reversibility of intraabdominal cryptorchidism, a study in which weanling rats were made artificially cryptorchid was undertaken. At the same time both sperm ducts were anastomosed into the urine bladder (vasocystostomy) to enable sperm output measurements, which were performed by putting the animals in metabolic cages for 24 hr. Group I animals were reoperated on 2 weeks after the initial cryptorchidism operation to reverse this intervention by an orchiopexy operation; in Group II orchiopexy was carried out after 4 weeks, in Group III after 8 weeks. In Group IV, a control group in which only the vasocystostomy operation was performed, the rats were sham operated. The animals were followed for 3 months after orchiopexy. All control animals showed sperm output between 20 and 30 million of spermatozoa per 24 hr from the age of 13 weeks on. However, experimental animals that had been de facto cryptorchid did not show any sperm output. Three out of 4 animals in which spontaneous descent of one or both testes had taken place showed sperm output from 6 to 8 weeks after orchiopexy. The results show that, notwithstanding the short periods of cryptorchidism, certain irreversible changes had already developed.

Artificial Intra-Abdominal Cryptorchidism in Young Adult Rats Leads to Irreversible Azoospermia

To study reversibility of artificial intra-abdominal cryptorchidism, in four groups of 5 rats at 3 months of age vasocystostomies (a microsurgical operation anastomosing both sperm ducts into the urine bladder) were carried out. This procedure enables sperm output measurements, which was performed by putting the animals for 24 h in metabolic cages. Four weeks later 15 of the remaining animals were operated again to induce artificial cryptorchidism. In a fourth group, 3 animals were sham-operated only, leaving the testes in place. Two weeks later in the animals of group I cryptorchidism was reversed by an orchiopexy operation; in group II orchiopexy was carried out after 4 weeks, in group III after 8 weeks. In group IV the animals were sham-operated again. Evaluation of sperm output took place for 3 months after orchiopexy. In the 1st week after vasocystostomy the animals showed a large variation in sperm output, but 2 weeks later, all animals had sperm output between 30-60 x 10(6) of spermatoza/24 h. Immediately after cryptorchidism sperm output decreased dramatically, and 2 weeks later all animals were azoospermic, except for sham-operated controls. After orchiopexy not one of the experimental animals showed any return of spermatozoa. We concluded that intra-abdominal cryptorchidism soon leads to irreversible damage to the testes resulting in azoospermia.

Abdominal Polyorchidism: An Unusual Variant

We describe an 18-month-old boy with polyorchidism in whom both ipsilateral testes were located intra-abdominally. To our knowledge no prior reports have documented a similar case in the literature to date. This case has important implications pertaining to the treatment of intraabdominal cryptorchid testes. Intra-abdominal polyorchidism and its management are discussed briefly.

Testicular Histology in Fetuses with the Prune Belly Syndrome and Posterior Urethral Valves

Intra-abdominal cryptorchidism and infertility are universal features of the prune belly syndrome but they usually are not seen with posterior urethral valves. To understand further the differences between these patients we reviewed testicular histology in 5 fetuses from each of 3 groups: prune belly syndrome, posterior urethral valves and normals. Spermatogonia were noted in all but the numbers were significantly reduced in those with the prune belly syndrome and posterior urethral valves compared to normals: 8.6 and 13.4 versus 31.2 per 10 high power fields, respectively. The fetuses with the prune belly syndrome also had marked Leydig cell hyperplasia in contrast to the other groups. These findings suggest that the testicular pathological condition in patients with the prune belly syndrome is caused by more than mechanical cryptorchidism.

Seminoma in undescended testes.

SUMMARY 1 Two cases of intra-abdominal seminomata arising from undescended testis are reported: Case 1.-A left ectopic testicular tumour presenting as a right-sided abdominal tumour simulating an appendix abscess. Case 2.-A right ectopic testicular tumour, presenting with pain in the right iliac fossa. 2 The importance of pre-operative diagnosis of intra-abdominal cryptorchid seminoma is stressed because early removal of the tumour followed by radiotherapy has a good prognosis.

Electroejaculation and evaluation of semen from the albino rat.

ArticleElectroejaculation and evaluation of semen from the albino rat.R L Lawson, G M Krise, and A M Sorensen JrR L Lawson, G M Krise, and A M Sorensen JrPublished Online:01 Jan 1967https://doi.org/10.1152/jappl.1967.22.1.174MoreSectionsPDF (929 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByTemporary intraabdominal cryptorchidism in the weanling rat leads to irreversible azoospermiaJournal of Surgical Research, Vol. 51, No. 2Vasocystostomy: A model for studying male reproductive toxicity in the ratReproductive Toxicology, Vol. 3, No. 3Effects of sympathetic denervation of rat internal genitalia on daily sperm outputUrology, Vol. 24, No. 6 More from this issue > Volume 22Issue 1January 1967Pages 174-6 https://doi.org/10.1152/jappl.1967.22.1.174PubMed6017641History Published online 1 January 1967 Published in print 1 January 1967 Metrics

CHORIONIC GONADOTROPIC EFFECTS ON HEIGHT AND OSSEOUS DEVELOPMENT IN SEXUALLY UNDERDEVELOPED YOUNG BOYS

IT is OBVIOUSLY necessary that those interested in chorionic gonadotropic therapy for sexually underdeveloped children be kept informed of the observations and results which are being affected in the field at the present time. In the past few years, several reports were made by this writer (I) on the good gonadal responses evoked through the use of gonadotropic therapy. It was also reported that there developed certain premature manifestations in some of the young children where gonado-tropic therapy was being given intensively in severe cases, particularly in cases of intraabdominal cryptorchidism. These evidences of precocity were manifested by the appearanc of suprapubic hair, hypertrophy of the phallus, priapism and ‘break’ in voice. At that time, it was stated that these precocious manifestations though undoubtedly undesirable were not to be considered as too serious and ought not to discourage the institution of gonadotropic treatment at an early age