Germ cell development in the descended and cryptorchid testis and the effects of hormonal manipulation

Germ cell development is an active process in normal testes during the first 4 years after birth, with transformation of the neonatal gonocytes into adult dark spermatogonia and then primary spermatocytes. The hormonal regulation of these changes is not fully understood, with evidence both for and against a role for gonadotrophins and androgens. Early surgical intervention in infancy aims to prevent or reverse germ cell maldevelopment. Although hormonal treatment for maldescent has been shown to be ineffective, there is still controversy over whether it may be useful as an adjunct to surgery to stimulate germ cells. Current evidence suggests that hormonal therapy may not stimulate transformation of neonatal gonocytes but may trigger prepubertal mitosis of primary spermatocytes. Further studies are required to determine the role of hormone treatment on germ cell development.Supported in part by grants from the National Health and Medical Research Council of Australia.     

Development and descent of the testis in relation to cryptorchidism

The testis descends in two phases. Animal studies suggest, that the transabdominal descent of the testis depends on the insulin-like hormone 3 (INSL3). Androgens are important in the inguinoscrotal testicular descent in animals and humans. In general, the cause of cryptorchidism is unknown and the aetiology is possibly multifactorial. Histological changes in cryptorchid testes demonstrate disturbed development. Conclusion: Since testicular descent is regulated by testis-derived hormones, cryptorchidism may reflect a functional defect of the testis.     

Testicular descent

Sixty male rats were treated twice weekly from birth with either oestradiol benzoate (E₂B) or sesame oil (controls) to see if oestrogen caused cryptorchidism by inhibition of gubernacular migration between 3 and 10 days after birth. Dissection was carried out at 10, 15, or 28 days, the processus vaginalis measured using a probe, and the weight of the testis recorded. The length of the processus was used as a measure of the length of migration of the hollow gubernaculum. Although E₂B affected testicular weight significantly at 15 days, the length of the processus vaginalis was not significantly different from controls during the normal time of gubernacular migration (3–10 days of age). Histology confirmed this observation, with the gubernaculum within but slightly higher in the scrotum in E₂B-treated males than in 15-day controls. Similar findings were found in a second group of 10 rats subjected to orchidectomy at birth to remove the androgen source. By 28 days all E₂B-treated animals were found to be cryptorchid, although the gubernaculum had completed its migration to mid-scrotal level. It is proposed that pubertal testicular descent in the rodent is inhibited by E₂B by mechanisms other than inhibition of gubernacular migration between birth and 10 days of age, which may be preprogrammed before birth.     

The vanishing testis

Surgical exploration of 417 clinically impalpable cryptorchid testes revealed 84 (20%) instances of absent testes. Thirty-five (42%) of the 84 explorations showed complete absence of the testes along with the epididymis and vas, whereas 49 (58%) were associated with blind-ending cord structures: the vanishing testis syndrome. The presence of a vas deferens and vessels lying side by side in the inguinal canal strongly suggests that a testis existed at one time and subsequently vanished, probably as a result of antenatal vascular accident. The incidence of vanishing testes in our patients was higher than the true congenital absence of testis including vas deferns and epididymis. Offprint requests to: P. Puri at the above address     

男童一侧睾丸缺失对另侧睾丸影响的研究

目的探讨男童一侧睾丸缺失后对另侧睾丸的生长、性激素水平及第二性征发育的影响。方法对61例一侧睾丸缺失的患儿进行随访,随访内容包括所剩睾丸体积、性激素水平及第二性征发育情况。同期检测150例各年龄段正常男孩相应指标。按≤10岁、10～12岁、〉12岁,分年龄段分别进行比较。结果各年龄段内,睾丸缺失组睾丸体积与对照组比较,差异均有统计学意义俨〈0．05）,睾丸缺失的不同疾病组之间比较,无统计学意义（尸〉0．05）;睾丸缺失早期另侧睾丸肥大明显,并随缺失时间延长而减轻;10～12岁及〉12岁组肥大尤为明显,与≤10岁组比较,差异有统计学意义（P〈0．05）;性激素水平随年龄增长而增加,但相同年龄段内,睾丸缺失组与对照组比较,差异无统计学意义（P〉0．05）;睾丸缺失患儿第二性征的出现及发育与正常儿童无明显差异。结论男童一侧睾丸缺失可致另侧睾丸代偿性肥大（CTA）。术后早期睾丸代偿增大更为明显;睾丸发育启动及增长发育期睾丸代偿肥大较处于相对静止期更为明显。但其增大程度与引起缺失的原发疾病无明显关系,且CTA不影响其后的性激素水平及青春期第二性征的出现。     

腹腔镜在未触及睾丸的隐睾中的应用

目的 探讨腹腔镜在未角及睾丸的隐睾中的诊断及治疗应用。方法 应用腹腔镜对１３例未触及睾丸的隐睾患儿作检查。术中发现腹腔内如有精索盲或发育差的精索,诊断为睾丸缺如;如发育好的粗索进入内环,做腹股沟探查;如睾丸位处于腹腔内,诊断为腹腔内睾丸,做分期Ｆｏｗｌｅｒ－Ｓｔｅｐｈｅｎ手术,或一、二期睾丸固定术等处理。结果 睾丸缺如６例（４６．２％）;腹腔内睾丸４例（３０．８）;睾丸于腹股沟３例（２３．１％）。     

外源性雌激素对小鼠睾丸引带收缩和增殖活性的影响

目的研究外源性雌激素(EEs)对胚胎小鼠睾丸引带组织肌动蛋白(Actin)和增殖细胞核抗原(PCNA)的表达以探讨EEs对睾丸引带收缩和增殖活性的影响。方法昆明雌性小鼠180只,随机分成18组,于孕9~17d每天分别给予DES、17α-E2、17β-E2和E3,每种药物又分别给予不同剂量25、50、100、200μg·kg-1·d-1和等体积的DMSO、生理盐水作空白和正常对照。孕19d处死母鼠,取出活胎,取其下腹部,常规固定、制片。应用免疫组织化学方法检测睾丸引带组织中肌动蛋白(Actin)和增殖细胞核抗原(PCNA)的表达。结果实验组小鼠睾丸引带组织发育较差,其中Actin含量降低,药物剂量越大,Actin含量越低(P<0.05);较大剂量(如200和100μg·kg-1·d-1药物组)的雌激素处理组胎鼠睾丸引带中PCNA含量降低明显(P<0.05)。两指标均有显著的剂量效应关系。结论EEs可随药物剂量的不同而不同程度地降低睾丸引带中Actin和PCNA的含量。表明EEs影响胚胎期睾丸引带的收缩和增殖活性,并可能是EEs影响睾丸引带甚或睾丸正常发育(下降)的机制。     

Antenatal torsion of the testes,a cause of vanishing testis syndrome

During the years 1976–1988, 412 patients were operated upon for cryptorchid testes. In 28 unilateral and 2 bilateral cryptorchid patients, no testes could be found. Pathologic examination of the blind-ended vas deferns (usually a nodule) in 6 cases showed calcified or hemosiderin-containing tissue. In 9 patients an abundance of blood vessels was noted. In 27 patients signs of fibrosis and/or hyalinization were found. It is postulated that in most instances the vanishing testis syndrome is due to in-utero vascular occlusion of the testicular vessels, which is most likely caused by torsion of the testis. Correspondence to: J. A. Bar-Maor     

Laparoscopic orchidopexy for the intra-abdominal testis

The role of laparoscopy in the management of the impalpable testis has been largely as a diagnostic tool only. Its therapeutic application as a single or two-stage Fowler-Stephens procedure for the intra-abdominal testis is assessed and a management algorithm derived. A retrospective review was performed of 26 children with 33 intra-abdominal testes (IAT) who were operated upon between 1992 and 1997; 5 had a single-stage (6 testes) and 21 had a staged approach. All children had the operated testis located in an acceptable scrotal position on review. Six operations were performed as a single-stage procedure. Four testes were palpably smaller at follow-up: 2 in the single-stage (33.3%) and 2 in the two-stage group (7%). Of the 26 children, 24 were day-case admissions. Minor self-limiting complications were observed in 5 cases. Laparoscopic localisation and Fowler-Stephens orchidopexy can be safely employed in the definitive management of the IAT. Accepted: 24 November 1998     

Crossed ectopic testis: a case report and review of the literature

Crossed or transverse ectopic testis is a rare anomaly of testicular descent. It has been noted that fewer than 100 cases have been reported in the world literature. In this paper, we report a new case found in a 6-month-old infant operated on in West Africa for an obstructed right inguinoscrotal hernia.     

Histological evaluation of the testicular nubbins in patients with nonpalpable testis: assessment of etiology and surgical approach

There is a controversy in the literature whether testicular nubbins carry malignancy risk and excision of the nubbin is necessary in patients with nonpalpable testis. It is also controversial whether vanishing testis has the same etiopathogenesis and risk with true undescended testis. The aim of this study is to investigate the histological findings of testicular nubbins in patients with nonpalpable testis and to question etiology and surgical indications for vanishing testis. We reviewed the histopathological results of 44 testicular nubbins in 40 patients (mean age: 4.1 years, range 1–13 years) with nonpalpable testis between 1992 and 2004, retrospectively. Exploration revealed 5 intraabdominal and 39 inguinal testicular nubbins. Of 44 specimens only 5 (11.3%) from inquinal testicular nubbins were found to have seminiferous tubules. Two of the five had seminiferous tubule structures with viable germ cells showing maturation correlating with age. The other two with scarce seminiferous tubules were seen on only a single area and one had Sertoli cells only. None of the excised tissue had malignant degeneration. The vas deferens was identified in 23 (52.2%), vessels in 26 (59%), calcification in 14 (31.8%) and hemosiderin in 12 (27.2%) of excised tissue. Presence of calcification in one-third of the nubbins supports vascular accident thesis in the etiopathogenesis of vanishing testis. The possibility for the presence of seminiferous tubules and viable germ cells in the testicular nubbin is low. These facts decrease theoritical risk of malingnancy. Therefore, an inguinal exploration for testicular nubbin in patients with vas deferens and vessels entering into the inquinal canal diagnosed at laparoscopy can be postponed untill testicular prosthesis implantation and the nubbin can be removed at this operation.     

Luteinising hormone releasing hormone for incomplete descent of the testis.

Forty boys with 54 incompletely descended testes took part in a double blind, controlled trial of intranasal luteinising hormone releasing hormone. In the control (placebo) group of 18 boys there was no significant change in testicular descent and all required orchidopexy; in the 22 treated boys, however, 12 of 29 testes (42%) were found in a lower position. This study supports the idea that a trial of intranasal luteinising hormone releasing hormone (1200 micrograms/day for 28 days) will help clarify the need for orchidopexy in at least 30% of boys with incomplete descent of the testis, particularly those in whom the testes have emerged from the inguinal canal.     

青春期精索静脉曲张对大鼠睾丸的影响与表皮生长因子的变化

目的观察青春期精索静脉曲张对大鼠睾丸的影响和表皮生长因子（EGF）的变化，探讨精索静脉曲张不育的机制。方法雄性wistar大鼠24只建立左侧精索静脉曲张模型作为实验组，18只为假手术组。术后4周、8周和12周采血并取双侧睾丸。光镜观察睾丸组织学变化并对生精功能评分；ELISA法测血清EGF浓度；RT-PCR法检测睾丸EGFmRNA表达。结果实验组睾丸重量减轻，生精功能受损，呈双侧性并进行性加重。术后8周实验组血清EGF水平显著低于假手术组（P〈0．01），4周和12周时差异无显著性意义（P〉0．05）。RT-PCR显示实验组左侧睾丸EGFmR—NA表达量术后4周（P〈0．05）、8周和12周（P〈0．01）均低于假手术组；右侧睾丸表达量术后8周（P〈0．01）和12周（P〈0．05）低于假手术组。结论青春期精索静脉曲张可使睾丸EGFmRNA表达量持续降低，引起睾丸发育障碍。     

Laparoscopyvs inguinal exploration for nonpalpable undescended testis

Objective : The optimal initial surgical approach for nonpalpable undescended testis (UDT) is debated. The aim of the present study is to compare the results of initial laparoscopy and inguinal exploration in the management of unilateral nonpalpable undescended testes.Methods : The results of 20 children with unilateral nonpalpable UDT managed by initial laparoscopy (group I) were compared with 20 age-matched children managed by inguinal exploration (group II). The location of testes and results of orchiopexy were compared in both groups. A single surgeon performed all the operative procedures.Results : The majority of testes (16/20 group 1,17/20 group II) in both groups were canalicular or low abdominal. Vanishing testes accounted for one-third (13/40) of the testes, the majority (85%) of which were located in the inguinal canal. All children were discharged within 24 hours of the operation. The success of orchiopexy at 4–6 weeks post-operatively was 85% and 86% in the two groups respectively. Retrospectively, only 7/40 (18%) of the testes would benefit from laparoscopy.Conclusions : Initial laparoscopic and inguinal approaches to nonpalpable UDT give comparable results. This report failed to demonstrate any specific advantage of initial laparoscopy in the majority of children with unilateral nonpalpable UDT.     

Effects of external inguinoscrotal compression on descent of the testis in rats

Intrauterine compression of the developing genitalia by the feet in early fetal development may be a cause of delayed descent of the testes. The purpose of our experiments on neonatal rats was to determine whether compression on the inguinoscrotum would impair testicular descent, which normally occurs during the 1st postnatal month. Two methods of compressing the inguinoscrotal region on one side were used: firstly, a ribcage graft from an inbred littermate was inserted subcutaneously in one series, and secondly, skin tightening was created by excising a wide area superficial to the gubernaculum and stitching the skin edges together longitudinally. Descent of the testis was retarded on the compressed side compared with both the non-compressed side and the sham-operated animals. The testes that had retardation of descent were smaller than those of the opposite side and of the sham-operated rats. It was concluded that experimental compression in rats may be akin to focal intrauterine compression in the human, causing delayed descent and changes in dimensions of the testes.This work was supported by grants from the National Health and Medical Research Council (Australia) and the Royal Children's Hospital Research FoundationOffprint requests to: F. D. Stephens     

The time relationship between ipsilateral testicular ischemia and germ cell apoptosis in the contralateral testis in rat

Unilateral testicular ischemia-reperfusion (IR) in the rat is followed by histologic damage in the contralateral testis, which has been previously explained on immunologic grounds. There is evidence to suggest that apoptosis in the contralateral testis is involved in germ cell loss following IR injury to the testis. We examined the time-dependent effect of testicular ischemia on germ cell apoptosis in the contralateral testis in a rat. Adult Sprague–Dawley rats weighing 250–280 g, were subjected to testicular ischemia for 1, 2, 3 or 24 h. Twenty-four hours following onset of the ischemic insult, testes were harvested for immunohistochemical studies. Apoptosis was detected using TUNEL immunohistochemical assay. Testicular ischemia in rats led to histological damage, which was related to the duration of the ischemia. In the contralateral testis, the minimal damage included a decrease in number of germ cell layers, mild disorganization, and single cell apoptosis. Apoptosis in the contralateral testes increased significantly after 2, 3, and 24 h of ischemia and showed direct, time-related correlation with the duration of ischemia. We conclude that testicular ischemia causes an increase in germ cell apoptosis in the contralateral testis. The extent of apoptosis increases with the duration of the ischemia.     

T-lymphocyte subsets in the contralateral testis after unilateral blunt testicular trauma in pre-pubertal mice

Although spermatozoa express antigens, they normally do not produce an immunological response because of the blood-testis barrier and the predominance of CD8⁺ T-lymphocytes in the rete testis. Unilateral blunt testicular trauma (UBTT) has been reported to decrease fertility. The present study was designed to evaluate the sub-populations of T-lymphocytes in mice with testicular trauma. Twenty male mice aged 20 days were randomized into control and test groups. At about 70 days of age the contralateral testis was harvested, cell suspensions were prepared, and immunofluorescence staining was performed for detection of CD4⁺ and CD8⁺ T-lymphocytes by flow-cytometry. The ratio of CD8⁺ and CD4⁺ lymphocytes was significantly higher (P < 0.001) in the control mice compared to the UBTT group (1.3 ± 0.3 vs 0.5 ± 0.01). The results suggest that UBTT alters the CD8⁺/CD4⁺ ratio in the contralateral testis, which may have an important bearing on the pathogenesis of infertility in cases of testicular injury. Accepted: 13 October 1998     

Laparoscopic versus open orchiopexy in the management of peeping testis: A multi-institutional prospective randomized study

ObjectivePeeping testis is an inconsistently palpable/seen undescended testis that migrates back and forth at the internal inguinal ring. Both open and laparoscopic orchiopexy are effective forms of management. The present study aimed to evaluate the efficacy and safety of both approaches.Patients and methodsBetween September 2007 and January 2012, 46 peeping inguinal testes were randomly treated with either open (25 cases) or laparoscopic (21 cases) orchiopexy procedures. Spermatic vessels were preserved for all cases. Operative details, postoperative morbidity and final testicular site and size were recorded.ResultsThe median age of the children was 2.5 years (range 0.5–12.0). The follow-up period ranged from 1.0 to 5.5 years. Of these testes, 20 in the open surgery group and 19 in the laparoscopic group maintained correct intrascrotal position (P = 0.428). Re-do orchiopexy was indicated for two cases in the surgical group (P = 0.493). No cases of testicular atrophy or hernia were encountered.ConclusionOpen and laparoscopic orchiopexy procedures for peeping testes are fairly comparable. However, laparoscopy is relatively more effective, as two re-do orchiopexies were required in the open surgical group.