Descent of the testis in the fetal calf. A summary of the anatomy and process

The descent of the testis in the fetal calf is reviewed, and the role in that process of the swelling reaction of the gubernaculum testis is discussed. The testes of 30 Dutch Friesian fetuses were examined by dissection and light microscopy of sections prepared from chemically and frozen-fixed specimens. The gubernaculum remains unattached to the scrotal fasciae until descent is completed. Shortening of the intra-abdominal gubernaculum and displacement of the testis begins at fetal week 11; the swelling reaction of the gubernaculum occurs between weeks 14 and 15. The testis is at the deep inguinal ring by week 15, and by week 20 it is in the scrotal position and the gubernaculum has regressed. It is proposed that the swelling of the gubernaculum dilates the vaginal ring and enlarges the inguinal canal. The clinical importance of these anatomical relationships and changes is discussed.     

B-mode ultrasonography of the bull testicle

The scrotum and testicles from 20 bulls aged 6 mo to 10 yr were obtained from a slaughterhouse and ultrasonically scanned to determine the normal echographic anatomy Ultrasonically, the normal bull testicle was homogeneous and moderately echogenic. The mediastinum testis was a linear structure in the center of the testicle and was slightly more echogenic than the parenchyma. The head and tail of the epididymis were easily identified on all testicles, but the epididymal body and ductus deferens were difficult to identify consistently. Ultrasound scanning of the testicles may prove to be a valuable noninvasive diagnostic technique for evaluating testicular diseases in bulls.     

Treatment of an undescended testis with human chorionic gonadotropin (HCG)

Seventy one patients with ectopic testis of age between 2 and 11.5 years were treated with human chorionic gonadotropin (HCG) at doses recommended by the International Health Foundation. The descent of testis to the scrotum was achieved in almost half of the treated boys (49.3%). The descent was successful mainly in cases of lower inguinal position of the undescended testicle, and only rarely when the testicle was situated higher. The descent was never successful in cases when the scrotum was small and underdeveloped.     

SURGICAL REPAIR OF UNDESCENDED TESTICLE

Orchiopexy by our method has given uniformly good results. We have had no direct nor indirect hernias after this dissection. We have had no complications attributable to the complete dissection we recommend. This dissection should give an increase in spermatic cord length averaging 6.5 centimeters. If the vas deferens is completely freed, an additional 2.5 centimeters of length is gained. This increase in length is four times that obtained by the routine classical dissections confined to the inguinal canal.All testicles absent from the scrotum should be transplanted by the sixth year. Earlier operation may be made necessary by troublesome hernia, pain, or torsion. Adequate incision, division of the floor of the inguinal canal, and retroperitoneal dissection assure good exposure. Division of the lateral spermatic ligament and elimination of the sides of the spermatic surgical triangles allow the testicle to exit from the external ring only. This will result in viable testicles in the depth of the scrotum, attached to intact blood supplies and vasa deferentia, and without tension, this giving the best chance to have normal spermatogenic testicles at puberty.     

La descente testiculaire

Gonadal development is intimately linked to that of the mesonephros. The primordial testes differentiate in the dorsal region of the embryonic abdomen, behind the coelomic cavity. To reach their final location within the scrotum, the testes descend into the pelvis, pass through the abdominal wall by the inguinal canal, and attach to the base of the scrotal pouch. Testicular migration therefore comprises three stages, each requiring its own mecanism (s). The genital ducts (epididymis, vas deferens) and ligament which attaches the testis to the scrotal wall (gubernaculum testis) certainly play an essential role in these migratory events. The first phase is quite passive, associated with the growth of the abdominal cavity. In the second phase, the gubernaculum enlarges and shortens, pulling the testis through the inguinal canal. Finally, the gubernaculum, as a short, fibrous ligament, attaches the testis to the scrotal wall.     

THE REPAIR OF DIFFICULT INGUINAL HERNIAS—Resection of the Spermatic Cord

A method of removing the cord structures from the inguinal canal and preserving the testis and the portion of the spermatic cord distal to the external ring was used in repair of large or recurrent hernias in 14 patients. Only one patient had pronounced testicular atrophy. In one case there was recurrence through the femoral canal. The procedure is simpler and shorter than removal of the testicle as well as the cord.     

Müllerian inhibiting substance production and testicular migration and descent in the pouch young of a marsupial

The ontogeny of Müllerian inhibiting substance (MIS) production by the developing testis of an Australian marsupial, the tammar wallaby (Macropus eugenii), was determined during pouch life using an organ-culture bioassay of mouse fetal urogenital ridge. This information was related to the morphological events during testicular migration and descent. MIS biological activity was found in testes (but not ovaries or liver) of pouch young from 2 to 85 days of age. MIS production had commenced by day 2, which is within a day of the first gross morphological signs of testicular differentiation. Müllerian duct regression occurred between 10 and 30 days, which partly coincided with testicular migration to the inguinal region and enlargement of the gubernacular bulb (15 to 30 days). These observations are consistent with the hypothesis that MIS may be involved in testicular transabdominal migration. The epididymis commenced development and growth only after the testis had descended through the inguinal ring. This provides no support for the suggestion that the epididymis is involved in testicular descent into the scrotum. The basic sequence of events in post-testicular sexual differentiation in the wallaby is sufficiently similar to that seen in eutherian mammals to make it an excellent experimental model for future studies of testicular differentiation, migration and descent.     

Abnormalities of testicular descent

Testicular descent occurs in two stages. The transabdominal phase (8–15 weeks) is controlled by enlargement of the caudal genito-inguinal ligament (gubernaculum) and regression of the cranial ligament. Insulin-like 3 from the Leydig cell appears to be the prime stimulator of gubernacular growth, augmented by Müllerian inhibiting substance/anti-Müllerian hormone. Testosterone causes regression of the cranial ligament. The inguinoscrotal phase (25–35 weeks) requires the migration of the gubernaculum from the groin to the scrotum; this migration is guided by the genito-femoral nerve releasing calcitonin gene-related peptide under the influence of androgen. The neonatal gonocyte transforms into a type A spermatogonium at 3–12 months of age, a step that is now known to be crucial for subsequent fertility, as the stem cells for spermatogenesis are created in this structure. This step is blocked in undescended testis and, hence, orchidopexy is currently recommended at 6–12 months of age. Congenital cryptorchidism is caused by the failure of gubernacular migration to the scrotum (1%–2%) but we now recognise that another 1%–2% of boys have acquired cryptorchidism, secondary to the failure of spermatic cord elongation with growth of the boy. These latter cases come to operation at 5–10 years of age. Surgery remains the mainstay of treatment, as hormonal therapy has not been proven to be effective, presumably because testicular descent is a complex anatomical mechanism.     

Basic morphological data of external genitals in 177 healthy Central European men

Five basic measurements were made of the penis, the scrotum and the testicles of 177 healthy Bohemian (Czechoslovakian) men, 18–20 years of age. The average length of the penis was 72.18 mm. The average circumference of the penis was 95.65 mm. The length of the right testicle was 47.37 mm, the length of the left was 45.17 mm. In 16.2% of those examined slight deformations of the urethral opening and mild malformations of the prepuce and the frenum were found. These defects did not disturb function. The method of measurement used has been described.     

Cryptorchidism in Florida panthers: prevalence,features, and influence of genetic restoration

The overall prevalence of cryptorchidism in Florida panthers (Puma concolor coryi) from 1972-2001 was 49% (24/49), with a significant increase over time. The earliest age at which descent of both testicles was known to occur was 2 mo and the latest was 10-13 mo. Delayed testicular descent was documented in 23% (8/35) of juveniles examined. Most retained testicles were in the inguinal canal. There was no apparent difference in reproductive success between cryptorchid and normal panthers, although no bilaterally cryptorchid panthers were known to have sired litters. Cryptorchidism was thought to be a manifestation of inbreeding and was one of several factors that led to the development of a genetic restoration plan whereby eight female puma from Texas were released into the panther population in 1995. None of the progeny resulting from genetic restoration efforts has been cryptorchid. This report provides evidence that cryptorchidism in panthers is genetically rather than environmentally based, and demonstrates the utility of genetic restoration for eliminating certain deleterious traits that result from inbreeding.     

Zur Ursache des Hodenabstiegs (Descensus testiculorum) bei Säugetieren1

On the cause of the mammalian descent of the testes (Descensus testiculorum) Two explanations have been offered for the descent of the testes in mammals, both of which are frequently cited in the literature. Moore and co-workers argued that the phylogenetic rise of body temperature caused the translocation of the testes. According to Portmann , the descent of the testes was due to the evolution of the scrotum as a signal. However, both the sensibility of the extra-abdominal testes to temperature elevations and the optical effects of the scrotum can be interpreted as a consequence of testicular descent rather than as its cause. The hypothesis presented in this paper suggests a new adaptive explanation for the descent of the testes in mammals and regards its development as an example of evolutionary compromise. Obvious disadvantages such as reduced protection of the extra-abdominal testes, “perforation” of the inguinal abdominal wall, and an increased loss of heat from the body core have to be outbalanced by a strong selective advantage. This advantage is seen in the development of a completely new, fast mode of locomotion - the gallop. The strong flexions and extensions of the vertebral column during gallop should cause intense fluctuations of intra-abdominal pressure. Fluctuations of intra-abdominal pressure severely impede continuous flow of blood in the abdominal veins. Periodically reduced venous drainage resulting in fluctuations of intra-testicular pressure would impair the process of spermiohistogenesis, which is dependent on an absolutely constant pressure within the testis. Thus, it is the displacement of the pressure sensitive testes out of the abdominal cavity that allows for the evolution of a fast mode of locomotion accompanied by strong fluctuations of intraabdominal pressure. In the course of the phylogenetic translocation of the testes increasing specializations of the testicular blood vessels occur. In mammals possessing a scrotum the return flow of venous blood from the extra-abdominal testes to the abdominal cavity is supported by utilizing the energy of the arterial pulse (‘peripheral arterial pump’). A model for the successive stages of the descent of the testes is illustrated in Figures 7–10. The morphological changes related to the phylogenetic descent of the testes, such as the specialization of the testicular blood vessels, the forming of a cremasteric sack in the inguinal region, and the differentiation of the inguinal or perineal integument into a scrotum can all be interpreted as serving one purpose: they aid in maintaining a constant intra-testicular pressure in spite of increasing fluctuations of intra-abdominal pressure and venous blood flow during the evolution of the gallop. Although the blood vessels of the spermatic chord basically serve the same functions, they show markedly different specializations in Marsupials and Eutherians. This indicates that the descent of the testes has occurred independently, at least, in these two groups. The explanation put forward here postulates a causal relationship between the mode of locomotion and the position of the testes. Mammals possessing testes wnich reside permanently within the abdominal cavity (‘Testiconda’) cannot gallop, whereas mammals with the ability to gallop must have (periodical or permanent) extraabdominal testes (‘Testiphaena’).     

Suppression of insulin-like3 receptor reveals the role of β-catenin and Notch signaling in gubernaculum development

During male development, the testes move from a high intraabdominal position and descend into the scrotum. The gubernaculum, an inguinoscrotal ligament connecting the testis to the lower abdomen, is believed to play a critical role in this process. The first stage of testicular descent is controlled by insulin like3 hormone (INSL3), produced in testicular Leydig cells. Deletion of Insl3 or its receptor, Rxfp2, in mice causes cryptorchidism. We produced Cre/loxP regulated shRNA transgenic mice targeting RXFP2 expression. We have shown that the transgene was able to reduce Rxfp2 gene expression and thus behaved as a hypomorphic allele of Rxfp2. Variable degrees of uni- and bilateral cryptorchidism was detected in males with the activated shRNA transgene on an Rxfp2+/- background. Conditional suppression of Rxfp2 in the gubernaculum led to cryptorchidism. Gene expression analysis of a mutant cremasteric sac using Illumina microarrays indicated abnormal expression of a significant number of genes in Wnt/β-catenin and Notch pathways. We have demonstrated profound changes in the expression pattern of β-catenin, Notch1, desmin, and androgen receptor (AR), in Rxfp2-/- male embryos, indicating the role of INSL3 in proliferation, differentiation, and survival of specific cellular components of the gubernaculum. We have shown that INSL3/RXFP2 signaling is essential for myogenic differentiation and maintenance of AR-positive cells in the gubernaculum. Males with the deletion of β-catenin or Notch1 in the gubernacular ligament demonstrated abnormal development. Our data indicates that β-catenin and Notch pathways are potential targets of INSL3 signaling during gubernacular development.     

Torsion of the testicle: a clinical review of 20 cases

Early diagnosis of testicular torsion is absolutely mandatory for salvage of a viable organ. The classical clinical presentation is a boy in the second decade with sudden onset of testicular pain accompanied by testicular tenderness and swelling as well as scrotal erythema and edema. The management is emergency exploration of the testicle with either orchiopexy or orchidectomy, depending upon the viability of the testis. In this series of 20 cases 90% had exploration with a salvage rate of 72%. Torsion of the testicle is in most cases due to a congenital abnormality; therefore contralateral orchiopexy is always done at the time of the exploration of the scrotum. The critical time interval from onset to exploration of the torsion is approximately 10 hours. In addition to the acute clinical entity, chronic torsion of the testis should be considered in all patients with unexplained orchalgia.     

Cryptorchidism in mice with an androgen receptor ablation in gubernaculum testis

Androgens play a critical role in the development of the male reproductive system, including the positioning of the gonads. It is not clear, however, which developmental processes are influenced by androgens and what are the target tissues and cells mediating androgen signaling during testicular descent. Using a Cre-loxP approach, we have produced male mice (GU-ARKO) with conditional inactivation of the androgen receptor (Ar) gene in the gubernacular ligament connecting the epididymis to the caudal abdominal wall. The GU-ARKO males had normal testosterone levels but developed cryptorchidism with the testes located in a suprascrotal position. Although initially subfertile, the GU-ARKO males became sterile with age. We have shown that during development, the mutant gubernaculum failed to undergo eversion, a process giving rise to the processus vaginalis, a peritoneal outpouching inside the scrotum. As a result, the cremasteric sac did not form properly, and the testes remained in the low abdominal position. Abnormal development of the cremaster muscles in the GU-ARKO males suggested the participation of androgens in myogenic differentiation; however, males with conditional AR inactivation in the striated or smooth muscle cells had a normal testicular descent. Gene expression analysis showed that AR deficiency in GU-ARKO males led to the misexpression of genes involved in muscle differentiation, cell signaling, and extracellular space remodeling. We therefore conclude that AR signaling in gubernacular cells is required for gubernaculum eversion and outgrowth. The GU-ARKO mice provide a valuable model of isolated cryptorchidism, one of the most common birth defects in newborn boys.     

Testicular organogenesis in the fetal calf: interstitial endocrine (Leydig) cell development

The development of the interstitial endocrine (Leydig) cells of the fetal testis in the calf is described and correlated with a swelling reaction of the gubernaculum and normal, prenatal descent of the testis. An hydroxysteroid dehydrogenase (HSD) procedure is used to determine the onset of functional activity for the interstitial endocrine cells (IEC). The NADH control procedure was strongly positive for the IECs at all ages investigated, indicating that these cells utilize the pyridine nucleotide as a coenzyme for oxireduction conversions. The 3 alpha- and 3 beta-HSD reactions were strongly positive and lightly positive, respectively, demonstrating that these cells contain the HSDs commonly utilized in the early steroidogenesis. TEM revealed structural evidence of this differentiating steroidogenic capability within IECs. During the period of the swelling reaction there is a functional IEC population, but there is no evidence presented by this study for a causal relationship of the gubernacular swelling reaction and subsequent normal descent of the testis into the scrotum.     

Cryptorchidie acquise, testicule oscillant et autres formes secondaires de cryptorchidie

Most of cryptorchidisms are due to failure in testicular descent during fetal life, but secondary forms of cryptorchidism exist. They are represented by cryptorchidism associated to general disease, ascended testis, retractile testis and iatrogenic forms. It is important to know and diagnose these forms, because histological lesions are present in any testis which stayed out of scrotum for a prolonged period.     

Infertility in a cryptorchid bull: a case report

A unilateral cryptorchid bull stationed in an AI center for 3.5 yr was studied to determine if maintaining such a bull could be justified. The following parameters were determined: quantity and quality of the ejaculates, basal and stimulated plasma testosterone concentrations, and the histology and testosterone concentrations of the testicles. The bull produced 232 ejaculates of which 125 (53.8%) were immediately discarded; the rest (107 ejaculations) were processed into pellets. Two of the 107 frozen ejaculates (2%) were found to be of excellent quality, 37 were (34.5%) of good quality, 45 were (42%) of satisfactory quality and 23 were (21.5%) of poor quality. Treatment of the calf with GnRH and hCG at 4 and 5 mo of age did not initiate the descent of the retained testicle. Testosterone concentrations measured at 14 mo, after hCG stimulus, indicated that the bull had impaired steroidogenesis when compared with 2 control bull calves. Post mortem examination revealed a small left testicle in the inguinal canal and a normal right testicle as well as normal secondary sex glands. During the breeding period at the AI center, the bull's peripheral testosterone concentrations decreased from 2.2 to 0.95 ng/ml Testosterone concentrations in the parenchymal tissue of the scrotal testicle were higher than in the parenchyma of the retained testicle (98.2 vs 53.9 ng/g). In contrast, the epididymis of the scrotal testicle had a lower testosterone concentration than the epididymis of the retained testicle (10.8 vs 33. 0 ng/g). On histological examination no spermatozoa were found in the retained testicle, the Sertoli cells showed fat degeneration, and fibrotic tissue surrounded the tubuli seminiferi. No pathological changes were found in the normal scrotal testicle. In conclusion, no justification was found for maintaining such a bull in the AI center for breeding purposes.     

Hormonal treatment for unilateral inguinal testis: comparison of four different treatments.

BACKGROUND: Hormonal treatment of cryptorchidism has been used since the 30s, but controversies persist on its efficacy. It is also unclear whether there are differences with the use of different hormonal trials. Aims: To evaluate the efficacy of four hormonal treatments on testicular descent in a homogeneous group of cryptorchid boys. PATIENTS: 155 patients (age 10-48 months) with unilateral inguinal palpable testis were studied. Methods: The patients were subdivided into four groups according to hormonal treatment: group 1 = hCG [500 IU/week (if the chronological age was <2 years) or 1,000 IU/week (if the chronological age was >2 years) for 6 weeks]; group 2 = hCG + hMG (hCG as in group 1 + hMG 75 IU/week for 6 weeks); group 3 = GnRH (1,200 microg/daily for 28 days); group 4 = GnRH + hCG (1,200 microg/daily for 28 days + 1,500 IU/week for 3 weeks, respectively). The results were evaluated at the end of the treatment period and 6 months later to exclude temporarily positive results. RESULTS: At the end of the hormonal therapy, scrotal testicular descent was present in 30 of 155 boys (success rate 19.3%). Seven testes relapsed during follow-up (23.3%). The long-term success rate was 14.8% (23/155 testes). No significant differences were observed in success rates as well as in relapse rates among the four groups. CONCLUSIONS: Hormonal therapy induced permanent testicular descent in a minority of young cryptorchid boys with inguinal palpable testis. Similar results were obtained with four different trials.