Torsion of the spermatic cord — A long term study of the contralateral testis

Summary The object of the present investigation was to study the long-term effects of the unilateral torsion of the spermatic cord on the contralateral testis. Eighteen guinea pigs were divided into 3 groups. In group I of six animals, unilateral torsion of the spermatic cords was maintained until the time of sacrifice. In group II of six animals, torsion of the spermatic cords was maintained for 8–12h, then the spermatic cords were untwisted and the animals were maintained until the day of sacrifice. Group III six animals, received an injection of pentobarbital, which served as control. All animals were sacrificed after 16 months. Extensive light and electron microscopic studies were carried out. In the contralateral testes of the experimental group of animals, several degenerative changes were noted, which included excessive intraepithelial vacuolization, a loss of germ cells and the presence of tubules containing only Sertoli cells and a few spermatogonia. 10.6% and 19.5% seminiferous tubules were damaged in the contralateral testes of torsion maintained and the torsion reversed groups of animals, respectively in comparison to 3.1% tubular damage (indicated only by occassional presence of intraepithelial vacuoles and necrotic germ cells), in the control testis. It was concluded that long-term effect of unilateral torsion of the spermatic cord is permanent and irreversible in nature.     

Unilateral torsion of spermatic cord in men: effect on Leydig cell

In our previous studies, we reported that short-term unilateral spermatic cord torsion had no adverse effect on the germ cells and the Sertoli cell in the contralateral testis of men. As an extension of our earlier investigations on the testicular pathophysiology in humans after unilateral spermatic cord torsion, the present study was undertaken to assess the Leydig cell function employing both fine structural and morphometric analysis in patients with short-term spermatic cord torsion. Bilateral testicular biopsy samples obtained from 4 men (15-19 years) with short-term unilateral torsion of the spermatic cord and from a control group of 6 men (15-40 years) were used in the present investigation. No appreciable difference in the Leydig morphology was noted between the biopsy samples from control and the contralateral testes. This was substantiated by morphometric analysis. The present study clearly indicates that patients with unilateral torsion of the spermatic cord may not essentially have bilateral testicular abnormalities, as suggested by the previous investigators. This report, thus lends further support to our earlier contention that alteration in microcirculation is quite likely the earliest and possibly the most significant contributor to the contralateral testicular damage in man after ipsilateral spermatic cord torsion.     

Ischemia,whether from ligation or torsion,causes ultrastructural changes on the contralateral testis

OBJECTIVE: Unilateral testicular torsion results with a decrease in contralateral testicular blood flow caused by a reflexive sympathetic response. The aim of this study was to investigate whether twisting of the spermatic cord, or testicular ischemia without twisting, activates this reflex mechanism and causes ultrastructural changes in the contralateral side. MATERIALS AND METHODS: Thirty adult male albino Wistar rats were randomly allocated into three groups of sham, torsion, and ligation. Right testes were twisted 720 degrees counterclockwise in the torsion group. Right spermatic cords were ligated permanently with a silk suture including the vas deferens in the ligation group. After 24 h of testicular ischemia, contralateral left testes were removed for electron microscopic evaluation. RESULTS: Contralateral testes showed similar ultrastructural changes in the torsion and ligation groups. The fibrous tunica propria enveloping the seminiferous tubule was thickened due to increased collagen fibers. The basal lamina was continuous but thickened and showed several foldings. The gap between basal lamina and the germ cells was increased because of collagen fibers. Leydig cells showed mitochondrial degeneration with the loss of its cristae. Leydig cells lost their contact with its neighborhood cells in some areas, and these gaps were filled with collagen fibers. Germ cells showed dilated cisternae of smooth endoplasmic reticulum, cytoplasmic electron-dense bodies and clear regions. CONCLUSIONS: Similar electron microscopic findings observed in the torsion and ligation groups indicate that testicular ischemia rather than twisting of the spermatic cord is responsible for the ultrastructural changes in the contralateral side.     

Immunohistopathology of the contralateral testis of rats undergoing experimental torsion of the spermatic cord

Aim:To evaluate the immunohistopathological changes in the contralateral testis of rats after an experimental sper-matic cord torsion.Methods:Male Sprague-Dawley rats of 45-50 days old were subjected to a 720° unilateralspermatic cord torsion for 10,30 and 80 days(experimental group,E),respectively or sham operation(controlgroup,C).Histopathology of the contralateral testis as well as germ cell apoptosis were studied using the TerminalDeoxynucleotidyl Transferase Biotin-dUTP Nick End Labeling(TUNEL)technique.The number of testicularlymphocytes,mast cells and macrophages,and the expression of tumor necrosis factor-α(TNF-α)and its receptor(TNFR1)in testicular cells of the contralateral testis were quantified by histochemistry and immunohistochemistry.TNF-α concentration in testicular fluid was determined by ELISA.Results:In the contralateral testis of rats fromthe E group,the maximal degree of damage of the germinal epithelium was seen 30 days after torsion.At this time weobserved in the E group vs.the C group increases:(i)the number of testicular T-lymphocytes;(ii)the number oftesticular mast cells and macrophages;(iii)the percentage of macrophages expressing TNF-α:(iv)TNF-α concen-tration in testicular fluid;(v)the number of apoptotic germ cells;and(vi)the number of TNFR1~ germ cells.Conclusion:Experimental spermatic cord torsion induces,in the contralateral testis,a focal damage of seminiferous tubulescharacterized by apoptosis and sloughing of germ cells.Results suggest humoral and cellular immune mediatedtesticular cell damage in which macrophages and mast cells seem to be involved in the induction of germ cell apoptosisthrough the TNF-α/TNFR1 system and in the modulation of the inflammatory process.(Asian J Andro12006 Sep;8:576-583)     

Is ipsilateral testis mandatory for contralateral testicular deterioration encountered following spermatic cord torsion?

Although deteriorating effects of unilateral spermatic cord torsion are generally accepted, the mechanism remains controversial. An experimental study was performed to evaluate the necessity of testicular and spermatogenetic material for contralateral testicular deterioration following unilateral spermatic cord torsion in rats. The animals were allocated to four groups: control, spermatic cord torsion, subepididymal orchiectomy, and spermatic cord torsion 14 days after subepididymal orchiectomy. The testes were removed on the 14th days and mean seminiferous tubular diameters and mean testicular biopsy scores were determined. Although contralateral testicular deterioration was more pronounced in the presence of testicular tissue, the absence of testicular tissue and/or spermatogenetic material did not prevent its occurrence. This is highly suggestive that autoimmune mechanism does not play a role in contralateral testicular damage following unilateral spermatic cord torsion.     

Exploration for testicular remnants: implications of residual seminiferous tubules and crossed testicular ectopia

PURPOSE: Testicular remnants identified during exploration for cryptorchidism contain vascularized fibrous nodules at the termination of the vas deferens, hemosiderin, calcification, a pampiniform plexus or occasionally residual seminiferous tubules that may contain germ cells. An absent testis lacks the features of testicular remnants. To our knowledge testicular remnants have not been described in a crossed ectopic location. We reviewed orchiectomy specimens obtained at exploration for a nonpalpable testis to characterize the features of testicular remnants, including the frequency of seminiferous tubules, germ cells and crossed ectopia, as well as to clarify the diagnostic criteria for testicular remnants. MATERIALS AND METHODS: From 1990 to mid 2000 medical records and histological slides from 101 boys with nonpalpable testes who had undergone inguinal exploration and orchiectomy were reviewed. RESULTS: Of the 71 testicular remnants identified 7 (9.8%) contained residual tubules, of which 4 (5.6%) contained germ cells. In 4 boys the testis was deemed absent but 3 did not undergo laparoscopic exploration. There were 2 ectopic remnants (2.8%) on the contralateral side-the pelvis or in the scrotum. Both crossed remnants demonstrated dissociation of the testis from the vas/epididymis which remained on the correct side associated with a pampiniform plexus. No müllerian remnants were encountered. CONCLUSIONS: Adequate exploration for nonpalpable testis requires laparoscopy with visualization of the contralateral pelvic region because an ectopic remnant may be dissociated from the vas/epididymis and vessels. Identification of a pampiniform plexus, vas and spermatic vessels may not be a reliable indicator of a testicular remnant. Continued removal of testicular remnants is warranted because at least 9.8% contain residual viable tubules.     

一侧睾丸扭转对对侧睾丸组织发育的影响

目的:研究一侧睾丸扭转以后对对侧睾丸组织的影响。方法:以大鼠为研究对象,按扭转时间及药物应用情况进行分组。在一侧睾丸扭转以后2个月,观察对侧睾丸曲细精管的变化。结果:一侧睾丸扭转2h以内,对侧睾丸曲细精管管腔和生精上皮增生;扭转6 h以后,曲细精管管腔和生精上皮萎缩;扭转6h以内应用别嘌呤醇能缓解对侧病变。结论:一侧睾丸扭转可以使对侧睾丸组织发育发生病理改变。     

Germ cell degeneration in the contralateral testis of the guinea pig with unilateral torsion of the spermatic cord. Quantitative and ultrastructural studies

This study evaluated the long term effects of unilateral torsion of the spermatic cord on the contralateral testis of guinea pigs, employing both fine structural and quantitative studies. Young, adult Hartley strain guinea pigs were divided into six experimental groups (12 animals per group). The first three groups consisted of 36 animals in which unilateral torsion was surgically induced. In group I (torsion maintained), unilateral torsion of the spermatic cord was maintained until the day of sacrifice; in group II (torsion and untwist), torsion of the spermatic cord was maintained for 8 to 12 hours, then the spermatic cord was untwisted and the testis was retained until the day of sacrifice. In group III (torsion and orchiectomy), testes were removed after 8 to 12 hours of spermatic cord torsion. The second three groups consisted of 36 animals: group IV (unilateral orchiectomy), group V (unilateral sham operation), and group VI (pentobarbital injection alone), which served as controls. One half of the animals from each group were killed after 4 months and the other half were killed after 8 months. The most frequently observed histologic changes in the contralateral testes of the experimental animals were focal disorganization and exfoliation of immature germ cells into the lumen. Severe damage, with almost complete absence of germ cells, was noted only in an occasional tubule. Quantitative evaluation of the germ cells of the contralateral testis revealed significant loss of germ cells in groups I, II, and III after 4 months, and in groups I and II after 8 months.(ABSTRACT TRUNCATED AT 250 WORDS)     

Diagnostic value of differential quantification of spermatids in obstructive azoospermia

Testicular biopsies from 80 azoospermic young men were revised and the average numbers per cross-sectioned tubule of each germ cell type were calculated and compared with those of control normal testes. In 53 patients, azoospermia had an obstructive cause, and in 22 of those 53 patients more adult spermatids were found by testicular biopsy than young spermatids (over 100% in some testes), in one or both testes. However, in normal testes fewer mature spermatids than young spermatids (23.3%) were found. In the 22 patients, the causes of azoospermia were: vasectomy (7 patients), bilateral agenesis of the vas deferens (3 patients), Young syndrome (3 patients), bilateral cysts in the caput epididymidis (1 patient), bilateral inguinal herniorrhaphy (1 patient), left varicocele (1 patient), and unknown causes (6 patients). Biopsies were bilateral except for 3 cases (a vasectomized patient, a patient with Young syndrome, and a patient with obstruction due to an unknown cause). Hormonal levels were normal in the 22 patients. In addition, testicular biopsies of 3 twisted testes from 3 young adult men showing a number of adult spermatids higher than that of young spermatids were also included in the study. All testicular biopsies-including those of the twisted testes-showed an obstructive histologic pattern, consisting of a mosaic distribution of testicular lesions: mainly tubular ectasis and germ cell sloughing into the adluminal compartment of seminiferous tubules. The increase in the number of adult spermatids was bilateral in 1 of the 6 vasectomized men who underwent bilateral biopsy, and in 7 of the 11 bilaterally biopsied patients with obstructive azoospermia due to other causes. The most probable explanation for the increased number of adult spermatids is stagnation of testicular fluid, caused by sperm excretory duct obstruction. The unilateral increase in the number of adult spermatids in vasectomized men might be related to the occurrence of a spermatic granuloma (a frequent finding in vasectomy) in the proximal end of the sectioned ductus deferens ipsilateral to the testis with nonincreased adult spermatid numbers, and the absence of spermatic granuloma in the ductus deferens ipsilateral to the testis with increased adult spermatid numbers. This granuloma would produce, in addition to spermatozoon destruction, reabsorption of the testicular and epididymal fluids. The higher rate of bilateral increase, in the number of young spermatids observed in the patients with congenital lesions of the ductus deferens or the ductus epididymidis, might be related to the absence of spermatic granulomas in congenital obstructions.     

Major differences between the testis and epididymis in the induction of granulomas in response to extravasated germ cells. I. A light microscopical study in mice

A spermatic granuloma is a chronic inflammatory lesion which surrounds extravasated spermatozoa. Clinically, the lesion develops in the interstitial spaces of the epididymis and vas deferens, and only exceptionally in the testis itself. In the present study, murine testes and epididymides were injured using a needle and the histological appearances of these organs was then compared. Traumatic injury induced extravasation of germ cells in both testes and epididymides. A few days later, spermatic granulomas consistently formed in the epididymides, however, such lesions were not induced in the testes. To examine the possibility that epididymal spermatozoa have inherently greater ability to form spermatic granulomas than do testicular germ cells, isolated epididymal spermatozoa or testicular germ cells were locally injected into the testes and epididymides of recipient mice. Spermatic granulomas readily formed in the epididymides after local injection of either epididymal spermatozoa or testicular germ cells. In contrast, such lesions did not form in the testes even when epididymal spermatozoa were injected. Therefore, this study suggests that the microenvironment of the testicular interstitium, rather than the extravasated components from the ruptured seminiferous tubules, is the main factor determining the limited formation of spermatic granulomas in the testis.     

The protective effects of nitric oxide on the contralateral testis in prepubertal rats with unilateral testicular torsion

OBJECTIVE: To investigate histological changes in the contralateral testis of rats with unilateral testicular torsion and the protective effects of nitric oxide (NO) on possible damage. MATERIAL AND METHODS: Twenty-eight prepubertal male Sprague-Dawley rats were divided into four equal groups. Group 1 underwent a sham operation of the right testis under general anaesthesia. Group 2 underwent a similar operation but the right testis was rotated 720 degrees clockwise for 6 h, maintained by fixing the testis to the scrotum, and saline infused during the procedure. Group 3 underwent similar torsion but L-arginine methyl ester (a precursor of NO) was infused during the procedure. In Group 4, NG-nitro-L-arginine-methyl ester, a NO synthase inhibitor, was infused separately during the administration of L-arginine methyl ester and torsion. All the left (untwisted) testes were removed from rats 21 days after surgery and evaluated histologically, assessing seminiferous tubule diameter, loss of sperm and spermatids, loss of germ cell layers, disarray of germ cell layers, rupture of tubules, Leydig cell proliferation and reaction in the ruptured tubules, and oedema. RESULTS: There was a significant difference in the indicators of histological damage between groups 2 and 4 and groups 1 and 3, except for the Leydig cell reaction in the ruptured tubules and oedema. The damage was significantly less in group 3 than in groups 2 and 4. CONCLUSION: These results suggest that long-term histopathological changes in the contralateral testes are important after unilateral testicular torsion and that NO has a protective effect on the contralateral testis.     

Laminin, type IV collagen, and fibronectin in normal and cryptorchid human testes. An immunohistochemical study

An immunohistochemical study of laminin, type IV collagen, and fibronectin was carried out in the testes of normal men and in the cryptorchid and contralateral scrotal testes of cryptorchid men from 2 to 40 years of age. The integrated optical density (IOD) per unit area of the lamina propria was measured in the immunostained sections. Fibronectin was found throughout the thickness of the lamina propria of the seminiferous tubules and in the interstitial connective tissue. No differences between normal and cryptorchid testes were found. Laminin was observed in the innermost part of the lamina propria of the seminiferous tubules and surrounding the endothelium of blood capillaries from infancy. No differences were found between normal and cryptorchid testes in the prepubertal period. In adult cryptorchid testes, laminin formed more numerous and deeper invaginations towards the seminiferous epithelium than in normal adult testes. Type IV collagen appeared throughout the thickness of the lamina propria of normal testes as well as in the wall of interstitial blood vessels. From infancy, the lamina propria of seminiferous tubules, but not blood vessel walls, showed lesser immunostaining for type IV collagen and a lower IOD of this component than did control tests from men of the same age. No differences between unilateral and bilateral cryptorchidism were found. The contralateral scrotal testes of cryptorchid males showed intermediate immunostaining for type IV collagen between that of normal control testes and that of cryptorchid testes. These findings suggest that the lamina propria of seminiferous tubules is lesioned at an early age in both cryptorchid and contralateral scrotal testes of cryptorchid men.     

Clinical aspects of testicular carcinoma-in-situ

Carcinoma-in-situ germ cells were demonstrated in testicular biopsies from 9 of 826 patients (1.1%) from a selected group of Danish infertile men. A similar observation was noted in testicular biopsies from 9 Swiss patients (representing 0.55% of the total number of infertile patients biopsied in that study). Such changes were also seen in 8 testicular biopsies from the contralateral testis of 180 patients (4.4%) with carcinoma of the teitis. Moreover, carcinoma-in-situ has beer, found in maldecended testes and in gonads of patients with the testicular feminization syndrome although the incidence of carcinoma-in-situ in these two latter groups is unknown.
The malignant potential of carcinoma-in-situ of the testis in infertile men has been clearly demonstrated, whereas its clinical significance in other groups of patients remains to be determined.     

Histological and immunohistochemical studies on the damage of contralateral testis following the unilateral testicular torsion in Wistar rats

The effect of experimental unilateral torsion of the testis on the contralateral intrascrotal testis in Wistar rats was evaluated histologically and immunohistochemically. The results were summarized as follows. 1) Histological damage of the seminiferous tubules in the contralateral testis was present only in adult rats. 2) The histological change 3-5 weeks after the experimental torsion consisted of marked decrease of spermatocytes, loss of spermatids and spermatozoa and numerous Sertoli-cell only tubules. Hyperplasia of the interstitial cells was demonstrated without thickness of the basement membrane and infiltration of the inflammatory cells. The tubular diameter and the ratio of contralateral testicular weight to rat body weight were significantly decreased (p less than 0.05) in torsion group. 3) Using an indirect immunofluorescent method, the positive immunohistochemical staining on spermatid and spermatozoa of normal testicular tissue was demonstrated using only the serum of rat with histological damage on the contralateral testis. Therefore, the phenomenon may be ascribable to the presence of antisperm antibody. It is concluded that the mechanism of the damage in seminiferous tubules of the contralateral testis with experimental torsion in adult Wistar rats is related to the humoral immunity producing antisperm antibody.     

Testicular lymphangiectasis in Noonan's syndrome

We describe a boy with testicular lymphangiectasis and Noonan's syndrome. Both testes showed seminiferous tubules with a reduced tubular diameter, containing few spermatogonia. The testicular interstitium exhibited a number of large, dilated lymphatic vessels forming irregular channels among the seminiferous tubules and surrounding them. Since there was no accompanying pathological condition to indicate an obstruction to the lymphatic flow at the level of the spermatic cord or in the regional lymph nodes, the abnormal development of testicular lymphatic vessels suggests a congenital malformation.     

Effects of unilateral testicular torsion on the blood flow of contralateral testis--an experimental study on dogs

The effects of unilateral testicular torsion on the blood flow of the contralateral testis were investigated. Fourteen adult male dogs were recruited. Seven dogs underwent unilateral testicular torsion of 4 h duration, and the other seven dogs had a control operation. Testicular blood flow was determined by colour Doppler ultrasonography before and after the testicular torsion. Bilateral orchidectomy was performed at the end of the study and histopathological changes were evaluated. Values of peak systolic velocity, end diastolic velocity, and resistive index were not statistically significant between ipsilateral and contralateral testes in the study group (p > 0.05). On comparison with the control group, blood flow in the contralateral testes showed no statistically significant difference (p > 0.05). Oedema and congestion were seen on ipsilateral testes in the study group. No histopathological changes were noted on the contralateral testes. Minimal oedema and congestion secondary to manipulation were found in the control operation testes. We conclude that unilateral testicular torsion does not decrease contralateral testicular blood flow as shown by colour Doppler ultrasonography.     

Ultrastructure of the seminiferous tubules in oligoasthenoteratozoospermic men associated with varicocele

Varicocele is associated with venous reflux that may cause increased heat and interstitial pressure within the testes, with variable pathological effects on spermatogenesis. This study aimed to study the ultrastructural testicular changes in the seminiferous tubules of 20 infertile severe oligoasthenoteratozoospermia (OAT) men associated with varicocele and five patients with obstructive azoospermia without varicocele as controls. They were subjected to testicular biopsy which was evaluated by transmission electron microscopy. Ultrastructurally, the seminiferous epithelium in the testicular biopsies of infertile severe OAT men associated with varicocele was variably affected in the form of thickening of the peritubular connective tissue, vacuolation of Sertoli cell and germ cell cytoplasm, presence of degenerated and apoptotic cells among the germinal epithelium, altered spermatids and abnormal spermatozoa. It is concluded that varicocele in severe OAT men is associated with ultrastructural changes in the seminiferous tubule.     

Quantitative evaluation of testicular biopsies from men with unilateral torsion of spermatic cord

Torsion of the spermatic cord is not uncommon among young men. Various abnormalities in the histology of the contralateral testis have been reported due to unilateral torsion of the spermatic cord. We quantitatively estimated the germ cells from three groups of men: normal individual (Group I), men with unilateral torsion of short duration (Group II), and men with unilateral torsion of long duration or some other condition such as varicocele or intermittent torsion to the contralateral testis (Group III). No significant difference in the number of spermatogonia, spermatocytes, and spermatids of Groups I and II patients was observed. This observation indicates that there was no pre-existing morphophysiologic defect in the testis of Group II patients. Severe damage in the contralateral testis was noted in Group III patients. This indicates that if a damaged testis is retained in the body for a long time, the contralateral testis may be affected. Contralateral testis may also be affected by intermittent torsion or varicocele.     

Activation of endothelial nitric oxide synthase in contralateral testis during unilateral testicular torsion in rats

There are controversies about the injury of the contralateral testis during unilateral testicular torsion (UTT). An autonomic reflex arc between bilateral testes has been proposed. The authors focused on the involvement of nitric oxide (NO) in the contralateral testis during UTT. Eight-week-old male Wistar rats underwent unilateral torsion (1 h)-detorsion (up to 24 h). NO synthase (NOS) activity was detected as NADPH-diaphorase activity after fixation by paraformaldehyde. N-nitro-L-Arginine methyl ester (L-NAME, 20 mg/kg) was injected intravenously to the other group of rats. To evaluate the testicular injury, proteolysis of alpha-fodrin production was detected by Western blotting. Apoptosis of the germ cells was evaluated by TUNEL. Long-term effect on spermatogenesis was evaluated by flow cytometry at 60 days after UTT. Transient activation of NOS was detected following the proteolysis of alpha-fodrin in the contralateral testis. L-NAME inhibited these alterations. NADPH-diaphorase activity and eNOS immunoreactivity were co-localized in the endothelial cells. These reactions were not observed in other organs. There was neither enhanced apoptosis nor deteriorated spermatogenesis in the contralateral testis during and 60 days after UTT. In the contralateral testis, eNOS-derived NO regulates the vasomotor function against unilateral testicular torsion, whereas it acts slightly cytotoxic. These results suggest the possible involvement of a testis-specific neurovasomotor reflex between the bilateral testes.     

Effect of testicular torsion on the contralateral testis and prevention of this effect by prednisolone

This study was instituted to evaluate the effect of unilateral testicular torsion on contralateral testicular histology and the prevention of this effect by prednisolone. Fifty Swiss albino rats were equally divided into 5 groups. In group 1, it was observed that, due to torsion, the mean seminiferous tubular diameter and percentage of spermatogenetic activity of the contralateral testes were reduced and an inflammatory reaction was also noted. In group 2, detorsion increased the above-mentioned damage, and in group 3, orchiectomy failed to prevent it. In group 4, it was seen that prednisolone slightly increased the mean percentage of spermatogenetic activity and produced proliferation of the Leydig cells in the intact testicle. In group 5, when prednisolone was injected just after torsion, no damage to the contralateral testes appeared. It has been thought that damage to the contralateral testes may arise from an autoimmune mechanism and prednisolone appeared to be very helpful in preventing damage by immunologic suppression.