[Teratoma in the orthoptic testis and in the ectopic precaval testis].
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Adolescent↗
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[Preservation of the tunica vaginalis propria testis in undescended testis].
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Child↗
Post-translational modification of proteins in the human testis development pathway.
BACKGROUND: The foetal testes produce the androgens necessary to masculinise the developing embryo and support the maturation of germ cells, that will eventually develop into sperm, thus ensuring future reproductive capacity. The testes develop from the bi-potential gonads in a highly orchestrated process resulting in the differentiation of a complex tissue with multiple cellular lineages. While recent transcriptomic and chromatin-based analyses of human foetal testes have provided an unprecedented level of insight into signalling pathways activated during this process, proteomic studies of the human foetal gonads remain limited. Proteins are active molecules and post-translational modification (PTM) of proteins influences protein activity, stability and localisation. Studies have shown that PTMs regulate critical proteins in testis development, and their disruptions are implicated in congenital disorders including differences of sex development (DSD), in which sex development is atypical. Despite this, the role and regulation of protein PTM during human testis development remains poorly understood due to limited access to human foetal gonadal tissue, a paucity of large-scale proteomics studies, and a lack of robust of human gonad in vitro models. OBJECTIVE AND RATIONALE: This review aims to provide a comprehensive analysis of validated PTMs affecting proteins critical for testicular development. We discuss PTMs with evidence for a role in normal testis development, and highlight those disrupted in DSD. We review emerging techniques, including proteomic technologies and organ modelling systems that may advance our understanding of PTMs in foetal testis development. We discuss challenges that have restricted the application of these technologies and how overcoming these will significantly improve our understanding of testis development and disease, diagnostics and patient outcomes. SEARCH METHODS: We searched PubMed and the University of Melbourne library for peer-reviewed English-language studies using keywords such as phosphorylation, SUMOylation, acetylation, ubiquitination alongside each protein of interest. PTM sites in proteins involved in testis development were identified using the PhosphoSitePlus database focusing those confirmed in in vitro or animal model studies. ClinVar and the Human Gene Mutation Database were used to identify patient variants that may disrupt PTM sites. OUTCOMES: Our review finds that proteins required for human foetal testis development are subject to extensive PTM. Several PTM sites and PTM-mediated pathways [e.g. MAPK (mitogen-activated protein kinase) pathway] are disrupted in patients with DSD or related conditions. While recent advances in proteomics technologies hold considerable promise, their application to human foetal gonads has been constrained by technical, ethical, and logistical challenges. Encouragingly, emerging high-sensitivity and low-input technologies, alongside stem cell-based approaches, offer viable pathways to overcoming these barriers. WIDER IMPLICATIONS: The relationship between gene regulation, protein expression, and cellular outcome is inherently non-linear, shaped by additional regulatory layers-most notably PTMs. The contribution of PTMs to human testis development in both typical and atypical contexts is a major knowledge gap. Addressing this gap has broad clinical and biological relevance: it may help improve genetic diagnosis or shed light on how proteins or pathways critical for testis development respond to environmental signals-an increasingly pressing question as declining global fertility rates bring testicular function under greater scrutiny. REGISTRATION NUMBER: N/A.
Humans↗
Clinical implications of gonadal venography in the management of the non-palpable undescended testis.
Selective gonadal venography was used on 28 patients with a total of 34 non-palpable undescended testes. The data obtained in this study suggest that 1) an internal spermatic vein with a pampiniform-like plexus indicates the presence of a testis, 2) a blind-ending vein on venography suggests the absence of a testis, 3) an internal spermatic vein or vas deferens may be present without a testis, 4) a testis probably cannot be present without a gonadal vein, 5) a testis may be present without a vas, 6) a blind-ending vas deferens does not necessarily indicate the absence of a testis and 7) a blind-ending vas deferens in a patient in whom a blind-ending gonadal vein is localized to the same region probably indicates the absence of a testis. Gonadal venography may localize a non-palpable undescended testis or suggest testicular agenesis. In addition, gonadal venography has aided in the selection of the operative approach and, in the future, may provide criteria under specific circumstances for determining whether an operation is necessary and, if so, the extent of surgical exploration.
Adolescent↗
Tissue guanosine-3',5'-cyclic monophosphate levels and soluble guanylate cyclase activity: a positive correlation during unilateral cryptorchidism in the rat testis.
The relationship between the subcellular distribution of guanylate cyclase and tissue guanosine-3',5'-cyclic monophosphate (cGMP) levels was investigated in rat testes after surgically induced unilateral cryptorchidism. Placement of one of a testis pair in the abdominal cavity results in loss of testicular weight and function in the abdominal testis whereas the remaining scrotal testis appears to be functionally normal. Within 5 days after surgery, tissue cGMP levels were increased by twofold in the abdominal testis. A fourfold elevation was noted from 10 to 30 days after surgery. Whereas the homogenate guanylate cyclase activity was only slightly elevated 10 and 20 days postoperatively, a 200% increase in the soluble guanylate cyclase activity was seen at 5 days. Between 10 and 30 days, the rise in activity was >250% (P < 0.01). An increase in soluble guanylate cyclase activity was noted when the data were expressed as per milligram protein, per milligram DNA or per whole testis. Conversely, particulate guanylate cyclase activity was reduced by 40% in the cryptorchid testis. Kinetic analysis of the soluble enzyme prepared from abdominal and scrotal testes yielded linear Line-weaver-Burke plots for both enzyme preparations with an identical K(m) for guanosine triphosphate, but a three-fold higher maximal velocity for the abdominal enzyme. When the soluble guanylate cyclases from both testes were mixed and assayed together, the activities were additive rather than exhibiting synergism or inhibition. These experiments indicate that the altered V(max) is not due to a transferable activator or inhibitor.An immunocytochemical technique was used to assess the cell type in which the alterations in cGMP metabolism occurred. Comparison of the scrotal and abdominal testes revealed that the abdominal testis exhibited enhanced cGMP immunofluorescence within the cells lining the inner aspect of the seminiferous tubule as well as tubular elements and interstitial cells. Thus, it is inferred that the correlated changes in soluble guanylate cyclase activity and cGMP levels occur in several of the cell types that remain viable within the cryptorchid testis.
Animals↗
Clinical implications of gonadal venography in the management of the non-palpable undescended testis.
Selective gonadal venography was used on 28 patients with a total of 34 non-palpable undescended testes. The data obtained in this study suggest that 1) an internal spermatic vein with a pampiniform-like plexus indicates the presence of a testis, 2) a blind-ending vein on venography suggests the absence of a testis, 3) an internal spermatic vein or vas deferens may be present without a testis, 4) a testis probably cannot be present without a gonadal vein, 5) a testis may be present without a vas, 6) a blind-ending vas deferens does not necessarily indicate the absence of a testis and 7) a blind-ending vas deferens in a patient in whom a blind-ending gonadal vein is localized to the same region probably indicates the absence of a testis. Gonadal venography may localize a non-palpable undescended testis or suggest testicular agenesis. In addition, gonadal venography has aided in the selection of the operative approach and, in the future, may provide criteria under specific circumstances for determining whether an operation is necessary and, if so, the extent of surgical exploration.
Adolescent↗
Testis antigens of man and some other primates.
Rabbit antisera raised aginst testis preparations of human, chimpanzee, rhesus monkey, and baboon origin were used to study testis-specific antigens within and among the four primate species. Antisera were absorbed with serum, liver, kidney, and spleen preparations of the respective species against which they had been produced. Immunoelectrophoretic analysis of testis extracts, using the absorbed antisera, indicated the following minimum numbers of testis-specific antigens for each species: man, 10; chimpanzee, 8; rhesus monkey, 10; and baboon, 8. Most of the testis antigens were cross-reactive among species. The results suggest that human spermatozoa possess at least four to five specific antigens which originate in the testis. The antigen that induces sperm-immobilizing antibody cross-reacted among the four species of primates. Human and rhesus monkey sperm reacted equally in the immobilization system. Testis extracts from each primate species were capable of removing the sperm-immobilizing activity of human immune sera by absorption. Testis proteinase activity, as determined by using a gelatin membrane substrate, was inhibited by the gamma-glogulin fractions of rabbit and rhesus monkey antisera and also appeared to be cross-reactive among the species.
Animals↗
[Tumours of the undescended testis (author's transl)].
It has now been clearly demonstrated that cryptorchidism is accompanied by a very marked increase in malignancy of the ectopic testis as well as in that in place. Amongst 80 patients undergoing surgery for carcinoma of the testis 14 (17.5%) had a past history of unilateral undescended. The risk of malignancy developing in an ectopic testis is 12 to 48 times greater than that of a testis which has descended normally. It would appear that the higher the position of the testis, the greater is the risk. Orchidopexy may decreased the risk if performed before the age of 11. When the tumour is situated in an ectopic testis, the clinical picture is often misleading. When the ectopic testis has been brought down the special feature of these tumours is the frequency of spread to inguinal lymph nodes. In terms of its basic principles the treatment of these tumours does not differ from that of those affecting normal testis. The aetiology of these tumours remains uncertain. There would seem to be a consensus in favour of a disgenetic origin, possible secondary to hormonal deficiency.
Adult↗
Torsion of the testis and allied conditions.
In 15 years at Bristol there have been 293 cases of torsion of the testis, 55 cases of torsion of a testicular appendage and 5 cases of testicular ischaemia due to other causes. The risk of a male developing torsion of the testis or its appendix by the age of 25 is about 1 in 160. Both conditions occurred primarily in adolescents, but among prepubertal boys torsion of an appendage was as common as torsion of a normally descended testis. There was a slight left-sided preponderance in testicular torsion, more marked in torsion of the appendages; the incidence of bilateral torsion was 2-0 and 1-8 per cent respectively. The clinical features and differential diagnosis of the two conditions are compared. Torsion of a testicular appendage is the most commonly misdiagnosed scrotal lesion, the preoperative diagnosis being correct in only 11 per cent of cases compared with 90 per cent for torsion of the testis. Twenty-one cases of recurrent torsion underwent prophylactic bilateral orchidopexy. There were 20 cases of torsion of undescended testes, with a salvage rate of only 20 per cent. The overall testicular survival rate was 55-3 per cent. Viability depends upon the possibility of spontaneous reduction, the preoperative delay after the onset of symptoms, the degree of torsion of the cord and the length of follow-up in doubtful cases. Urgent scrotal exploration is advised in every case of acute testicular pain unless there is overwhelming evidence of epididymoorchitis. Exploration of the opposite side is mandatory in torsion of the testis and advisable in torsion of an appendage.
Adolescent↗
[Surgical technique in the management of undescenced testis (author's transl)].
In cases of retentio abdominalis or inguinalis and of ectopic testis, surgery is performed about the 2nd year of life. Essentials of the operating technique are: incision of the skin must not be parallel to the spermatic cord; testes and spermatic cord must be mobilized without trauma; ideally a biopsy of the testis should be taken; any pulling of the spermatic cord and torsion of it during fixation of the testis should be avoided. If initial tensionfree placement of the testis in the scrotum is impossible, the operation should be carried out in 2 sessions with an interval of 6-12 months. In 241 cases of children operated on from 1972-1975 with 308 total operations, the author observed 2 recurrences and 1 deep infection (scrotal abscess).
Adolescent↗
[Long-term study on the influence of running exercise, food restriction, running exercise + food restriction and of parenterally applicated testis cells on age-parameters of the rat (author's transl)].
Preliminary results of a long-term study on 1100 male Sprague-Dawley rats are presented, showing the influence of running exercise, of restricted diet, of both of these together and of the s.c. application of lypholized testis cells. Up to now animals aged 9, 15 and 24 mths were investigated. The test-animals were exposed to the experimental conditions from their 6th month of life. The running exercise was carried out on a treadmill (30 m at a speed of 25 m/min, horizontal) 5 days a week. A food restriction of about 20% was achieved by 2 fasting-days a week. The lyophilized testis cells were injected for the first time at an age of 9 mths and afterwards in 6 mths intervals. Between the injection and the assessment of the age-parameters there was an interval of 6 mths. S o fare the following parameters of the comprehensive test-program have been evaluated: 1) running performance in m (treadmill, 20 m/min, ascent 15 degrees), 2) motor activity (Animex Activity Meter), 3) chemical contraction-relaxation of tail-tendon-fibers, 4) total lipids and total cholesterol in the plasma. The results obtained so far show that a mild regular training, moderate food restriction and the s.c. application of testis-cells are able to cause a significant shift in the dirction of a younger biological age in at least some of the age parameters. The action of the testis-cells seems to affect most of the age parameters but shows the tendency to be more distinct at a higher age. More concrete statements about the influence on the biological age or the vitality will only be possible after the multivariate analysis of the results.
Age Factors↗
Agenesis or atrophy of the testis and vas deferens.
In this study the author examines the relationship between agenesis or atrophy of the testis and of the vas deferens. From a prospective study of 237 cases of unilateral and bilateral undescended testis, 12 cases of agenesis of a testis were seen; 9 of the 12 cases were associated with agenesis of the vas deferens and in 3 of these unilateral renal agenesis was also present, not necessarily ipsilaterally. Three other cases of testicular agenesis and four cases of extreme testicular atrophy were seen. In all seven, the vas deferens was present in part or in its entirety and roentgenography disclosed a normal upper urinary tract. Agenesis of the vas deferens was seen only in patients with monorchism. No patient was anorchid. It is concluded that an important link exists between agenesis of the vas deferens and agenesis of the testis.
Abnormalities, Multiple↗
Two rare cases of ectopic testis.
A case of pubopenile testis and a case of perineal ectopic testis are presented. The mechanism of descensus is largely positive, possibly facilitated by raised intra-abdominal pressure. The testis is usually guided by the gubernaculum and ectopia results from gubernacular failure. The ectopic testis is relatively rare but is easily recognized and treated by orchiopexy.
Child, Preschool↗
Cryptorchidism, hernia, and cancer of the testis.
Risk of cancer of the testis was related to nondescent and hernia in a comparison of 596 testicular cancer patients and 602 unaffected men who had been in active service in the U.S. Army between 1950 and 1970. Medical histories were obtained from routine service records. Undescended testis was associated with a testicular cancer risk 8.8 times that of normal. Among cancer patients with a history of undescended testis, seminomas were nearly twice as frequent as in the remaining patients. Of 14 patients with unilateral undescended testis, 12 had the tumor on the side of the defect. Testicular cancer risk was estimated to be 2.9 times higher in men who had reported having had an inguinal hernia than in those who had not. Side of hernia and side of tumor were not associated; histologic type was not related to history of hernia.
Cryptorchidism↗
Carcinoma in situ of the ectopic testis.
A young man with a palpable ectopic testis underwent right testis biopsy and orchiopexy. Since histological findings of the biopsy specimen revealed an unsuspected intratubular carcinoma in situ and evidence of diminished spermatogenic potential, an inguinal orchiectomy was done. This appears to be the first reported case of a tumor of this type developing in an undescended testis.
Adult↗
Response to cryptorchidism of the testis and epididymis of the opossum (Didelphis virginiana).
Adult male opossums, Didelphis virginiana, were rendered hemicryptorchid for 35 days. The cyrptorchid testis exhibited a significant reduction in weight, while the contralateral testis had a compensatory weight gain compared with testes of untreated animals. Histological changes in the cryptorchid testis included fibrosis of the tunica propria, involution of the seminiferous tubules and an apparent increase in the interstitial tissue. Many seminiferous tubules were empty and germinal cells were absent. Some Sertoli cells persisted, but the cytoplasm was vacuolated. Cryptorchid testes were characterized by mononuclear leucocytic invasion around the tubules, and some eosinophils were observed. Cryptorchidism in the opossum may induce a reaction similar to experimental orchitis.
Animals↗
Testicular venography in the nonpalpable testis.
Localization and identification of a nonpalpable testis can be done accurately by testicular venography. The identification of the pampiniform plexus is essential to the localization of the testis by this method. We evaluated 15 patients 3-39 years of age with 21 nonpalpable testes. Fourteen successful testicular venograms were performed showing four retroperitoneal testes, four testes within the inguinal canal, and two testes located in the superficial inguinal pouch. Three nonpalpable testes were thought to be due to true agenesis, and one venogram was performed after prior surgical removal of the testis. Catheterization of the left testicular vein was accomplished with greater ease and accuracy (79%) to the right side (42%).
Adolescent↗
Current concepts of the undescended testis.
Abnormalities of testicular descent represent the most common genitourinary anomaly in men. Many aspects of testicular maldescent remain controversial. The etiology of the undescended testis is still not known, but results of experimental work in rats strongly support the hormonal theories. Distinction between the truly undescended testis and the retractile testis remains a problem, making retrospective analysis of previous data confusing. Newer aspects of diagnosis of nonpalpable testes include the human chorionic gonadotropin test, herniography, venography and arteriography. Routine aspects of surgical therapy have changed little in recent years, although newer techniques, such as microsurgical procedures and innovative scrotal anchoring methods, are now available. Malignant tumors and infertility are the most worrisome complications. Evidence is presented to suggest that prognosis is related not only to choice of therapy but also to its timing. The recent evidence for Sertoli cell dysfunction, if substantiated may resolve some of the controversies.
Chorionic Gonadotropin↗