Immunologic aspect of testicular torsion: detection of antisperm antibodies in contralateral testicle

OBJECTIVE: To evaluate the immunologic etiology in unilateral testicular torsion, an experimental study in rats was carried out. MATERIALS AND METHODS: 75 adult Wistar rats included in the study program were divided into six different groups according to a torsion-detorsion procedure. Torsion degree was kept constant for all animals (720 degrees ). Anti-rat immunoglobulin G (IgG) antibodies against spermatozoa antigens were identified in contralateral testicular tissue after 1 month following detorsion and/or orchiectomy of the twisted testicle. RESULTS: We revealed antibody formation in animals subjected to unilateral torsion for 12 and 24 h, which then followed by detorsion of the testicle. IgG was identified especially on basal membrane of the tubules. CONCLUSIONS: As the controversy on the exact mechanism of testicular damage in unilateral torsion still continues, our findings showed that a possible immunological etiology may play an important role in this respect.     

The effects of unilateral testicular ischemia and hemicastration on contralateral testicular IGF-1 level,histology and lipid peroxidation

Hemicastration is followed by compansatory hypertrophy whereas unilateral testicular torsion is followed by atrophy in contralateral testicle in rats. Insulin-like growth factor (IGF-1) has important roles in testicular paracrine and autocrine functions. In this study it was aimed to compare ischemic parameters and IGF-1 levels in the contralateral testicle in unilateral spermatic cord ligation, testicular torsion, and hemicastratron. 32 wistar rats were equally altocated into sham, ligation, torsion, and hemicastration groups. In ligation group, right spermatic cord was ligated with 3/0 silk suture. In the torsion group, right testis was tcrsed for 720 degrees. In hemicastration group, right orchiectomy was done. 48 hours later left orchiectomy was done in all groups. Malondialdehyde (MDA) and IGF-1 levels were determined in the testicle. Average values of the groups were compared with Anova followed by Dunnett T3 multiple comparison tests. MDA levels were significantly reduced in ligation and torsion groups (p < 0.05). This reduction was more prominent in hemicastration group (p < 0.05). Contralateral testicular IGF-1 levels in ligation and torsion groups were not different compared with the sham group. Left testicular IGF-1 level in the hemicastration group was decreased significantly compared with other groups (p < 0.05). Histological. changes evaluated. Contralateral Johnsen's testicular biopsy scores were significantly decreased in all experimental groups but mean tubular diameter was not changed in all groups.     

Unilateral testicular torsion: protective effect of verapamil on contralateral testicular histology.

In this experimental study, it was our aim to reduce the effects of ischemic insults to the contralateral testicle after unilateral testicular torsion. The protective effect of a calcium channel blocking agent (verapamil) on the histology and the tubular diameter of contralateral testicle was evaluated. Following a definite period of unilateral testicular torsion (i.e., 4 h), the protective effect of this specific medication was evaluated both after detorsion and orchiectomy procedures. The results of our study demonstrated the protective effect of verapamil on both parameters, especially in animals undergoing orchiectomy. The majority of the specimens demonstrated normal histologic findings together with preserved tubular structures after a 1-week period under verapamil medication.     

The effect of testicular torsion on the contralateral testis and the value of various types of treatment

In an attempt to investigate the effect of testicular torsion and various forms of treatment on the contralateral testis, an experimental study on rats was undertaken. The first group comprised control animals. In the second group the left testes were twisted 720 degrees and the right testes were removed 4 weeks later for histopathological examination. In the third group the rats were subjected to a left detorsion procedure 24 h after torsion, while in the fourth group cortisone treatment was added to the above procedure. The fifth group consisted of rats which had undergone left orchiectomy 24 h after torsion and the sixth group had cortisone treatment plus orchiectomy after torsion. Cortisone treatment was started 24 h after testicular torsion and continued for 4 weeks. Histopathological examination of the contralateral testes which were removed 4 weeks later showed that either orchiectomy plus cortisone or detorsion plus cortisone was more successful than other forms of treatment.     

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.     

Experimental testicular torsion and its effects on the contralateral testicle

Objective Following experimental unilateral torsion of the testis the histologic effects of unilateral testicular torsion on the contralateral testis were investigated. Materials and methods Utilizing detorsion or orchiectomy at 4 hours and 8 hours after torsion, the effects of early and late treatment modalities on the contralateral testicle were observed. Results Morphometry of the contralateral testis revealed some alterations including focal sclerosis, decrease in mean seminiferous tubular diameter and a marked increase of the Leydig cells in some subgroups. Conclusion In spite of some changes, definite evidence for contralateral damage due to ipsilateral torsion contributing to male infertility was hardly observed.     

The effects of human chorionic gonadotropin treatment on the contralateral side in unilateral testicular torsion

BACKGROUND/PURPOSE: Unilateral testicular torsion can cause histologic damage, consisting of aspermatogenesis and tubular atrophy, in the contralateral testis human chorionic gonadotropin (HCG) treatment is widely used in undescended testis, and has been shown to improve histomorphometric alterations beside the testicular descent. However, the role of HCG in testicular torsion has not been investigated before. Therefore, this experimental study was conducted to evaluate the effects of HCG treatment on contralateral testicular histology and function in unilateral testicular torsion. METHODS: Forty adult male Wistar rats were randomized into 4 groups: SHAM, SHAM+HCG, TORSION, and TORSION+HCG. Torsion was created by twisting the righ testis 720 degrees and maintained by fixing it to the scrotum. HCG treatment started 24 hours after the torsion at a dose of 100 IU/kg, twice weekly for three weeks. Left orchiectomy was performed one month after the torsion and removed testes were immersed in Bouin's fixative for histopathological evaluation. Mean seminiferous tubule diameter (MSTD) was measured and Johnsen's score was calculated. Blood samples were taken for assaying serum testosteron level. RESULTS: Unilateral testicular torsion resulted in a significant decrease in spermatogenesis and MSTD on the contralateral side. Serum testosteron level was also reduced. HCG treatment improved these parameters in the contralateral 'untwisted' testis beside the serum testosteron. CONCLUSIONS: Our data demonstrates that unilateral testicular torsion adversely effects its counterpart. HCG treatment improves contralateral histomorphometric alterations and serum testosteron in unilateral torsion.     

Testicular torsion: Evaluation of contralateral testicular histology

Infertility may occur in patients with unilateral testicular torsion whose contralateral testis is intact. Depending on this observation, the physicians have begun to examine the contralateral testis. In the present prospective study we aimed to examine the histopathologic alterations occurring in the contralateral testicle with time. Sixty adult male albino rats were included in the programme, and following experimental torsion the histopathologic findings, especially those in the contralateral testis, were evaluated after 4–12 weeks. Long-term and high degree torsion of the testicle led to varying degrees of deterioration in the germinal epithelium and interstitial cells of the contralateral testicle. Histopathologic alterations were reversed in 12 weeks. Tubular diameter and testicular volume also decreased in accordance with the histopathologic alteration. In our opinion, orchiectomy following torsion of one testicle will limit potential histopathologic alterations in the contralateral testicle.     

Antisperm autoantibody response after unilateral vas deferens ligation in rats: when does it develop?

Unilateral obstruction or injury to the vas deferens can result in significant injury to the contralateral testicle. Antisperm autoantibodies are thought to play a significant role in this phenomenon. It has been reported that early surgical repair of the vas, before the development of antisperm autoantibodies, will prevent any potential damage to the contralateral testicle. This led us to investigate the timing of the antisperm antibody production and to attempt to determine whether antibody production precedes histologic testicular damage in the Lewis rat model. In a controlled study, mature rats were divided into temporal groups, with the experimental animals all receiving a unilateral vasectomy. At postoperative endpoints of 1, 7, 15, or 30 days, blood samples were collected for immunologic assay, and the testicles were harvested for histologic examination. Antibody levels were measured by an immunobead test using goat anti-rat immunoglobulin G (IgG)-coated Sepharose beads; tissue sections were fixed in Bouin solution, embedded in paraffin, and stained with hematoxylin and eosin. There was no statistically significant histologic difference between any of the groups. However, immunologic evaluation revealed a statistically significant increase in immunobead antibody binding in the 30-day group compared to the control groups (P = .02). These data seem to indicate that in this model, antisperm antibody production is not evident until 15-30 days after unilateral injury to the vas deferens occurs, and the development of these antibodies precedes any demonstrable histologic damage to the testicle. If it is correct to infer that human antisperm antibody production will also precede histologic testicular damage, and further, that the onset of the human autoantibody response may vary from several days to weeks, then in cases of suspected or known ductal injury, the clinical monitoring of antisperm antibody levels could enable testicular damage to be predicted prior to its development and thus be avoided.     

A case of testicular infarction in the newborn

A 6-day-old male was pointed out to have right intrascrotal swelling at birth. Surgical exploration did not reveal torsion of the spermatic cord. The testicle was suspected to have a malignant tumor and then right inguinal orchiectomy was performed. Orchiopexy of the contralateral testicle was not performed due to lack of torsion. Histological examination showed coagulation necrosis of the testicle. Sixty-three cases of testicular infarction in the newborns including our case from Japanese literature were reviewed and discussed.     

New animal model to evaluate testicular blood flow during testicular torsion.

BACKGROUND/PURPOSE: Unilateral testicular torsion is known to cause infertility because of damage to the contralateral testis. Testicular damage has been attributed to many different mechanisms, one of which is altered contralateral blood flow. In our experiment, in an effort to identify the reason for contralateral testicular injury, the authors developed an accurate method of measuring blood flow in both testes before, during, and after unilateral torsion. METHODS: Four- to 6-week-old piglets weighing 4 to 6 kg were studied. The animals were anesthetized, intubated, ventilated, and catheterized for vascular access. Piglets were assigned randomly to a sham group or a group undergoing 360 degrees or 720 degrees torsion of the left testis (n = 5 per group) for 8 hours, after which it was untwisted. Data were collected at baseline (T = 0), 8 hours of torsion (T = 8), and 1 hour after detorsion (T = 9). Mean arterial blood pressure and heart rate were monitored continuously. Testicular blood flow was determined using radiolabeled microspheres. Blood flow data were evaluated by analysis of variance. RESULTS: In the 360 degrees torsion group, blood flow changes were insignificant during torsion and after detorsion. In the 720 degrees torsion group, blood flow to the twisted testis was reduced significantly, whereas the contralateral testis was unaffected. One hour after detorsion, blood flow to both testes was increased significantly. CONCLUSIONS: The authors describe a new animal model to evaluate testicular blood flow during and after testicular torsion. Increased blood flow after detorsion may be the cause of testicular damage in patients with unilateral testicular torsion.     

【原创论文】同侧和对侧大鼠睾丸缺血再灌注损伤的生化效应和褪黑激素对此的保护作用

睾丸扭转（TT）,是一个多发于青春期男性的泌尿急症,如果不及时治疗,可致不孕不育。睾丸扭转所致缺血再灌注（I／R）损伤在睾丸损伤的病理生理过程中起一定作用。我们研究了褪黑激素在单侧睾丸扭转大鼠中同侧和对侧睾丸的氧化损伤效应：将21只青春期雄性Wistar大鼠分成三组,每组七只,处理如下：第1组（假手术组）：行左睾丸和双边睾丸假切除术;第2组（I/R组）：通过以下方式诱发缺血再灌注损伤（顺时针720°旋转左侧睾丸2小时,2小时后复位）：第3组（I／R＋MEL组）：大鼠经诱导缺血再灌注损伤和一次性褪黑激素注射（50mgkg-1,i．p）。处理后离体分离各组大鼠双侧睾丸,用于检测睾丸组织中抗氧化过氧化氢酶、超氧化物歧化酶和谷胱甘肽过氧化物酶的活性,丙二醛、蛋白质羰基和一氧化氮的组织水平。较对照组,褪黑激素注射组同侧睾丸的脂质过氧化水平,相关酶活性降低,具有显著性（P〈0．05）,而在对侧的睾丸中相关酶活性变化无统计学意义（P〉0．05）。在对侧睾丸中,丙二醛水平改变具有明显统计学意义（P=0．009）。应用褪黑素能减轻老鼠同侧睾丸扭转所致缺血再灌注损伤的不利影响,而对于对侧睾丸,睾丸扭转影响不大。     

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.     

Effect of external scrotal cooling on the viability of the testis with torsion in rats

BACKGROUND AND AIM: Testicular damage due to ischemia during torsion is aggravated after reduction and reperfusion. The severity of the damage depends on the degree and duration of the torsion. Hypothermia has been successfully used in preserving the viability of ischemic organs for a prolonged period. Our aim is to evaluate the effect of external scrotal cooling in preserving testicular viability after spermatic cord torsion in rats. METHODS: 100 adult male Sprague-Dawley rats were equally divided into ten groups. Exposure of the right testicle for either 4 or 8 h in groups 1 and 2 were the control groups. The rats in eight groups (3-10) underwent clockwise torsion of 1,080 degrees of the right testis around its longitudinal axis, for either 4 or 8 h. External scrotal cooling was applied during the torsion period in four groups. Half of the rats were sacrificed at the end of the torsion period, while the other rats underwent detorsion and were sacrificed 2 weeks later. All testicles were excised for histology. RESULTS: The histological results showed that external scrotal cooling decreased both immediate and late damage to the testis, caused by torsion. A moderate degree of injury was found in the contralateral testicle in rats after torsion of the right testicle for 8 h with application of external cooling and detorsion. CONCLUSION: External scrotal cooling is effective in preserving the viability of the torsed testis in rats. The injury of ischemia-reperfusion, although reduced by external cooling, may endanger the contralateral testis as well, if the duration of torsion is longer than 4 h. With increased duration of torsion, orchiectomy should be considered. Application of this treatment may reduce the injury in humans awaiting surgery.     

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.     

Evaluation of contralateral testicular damage after unilateral testicular torsion by serum inhibin B levels.

BACKGROUND/PURPOSE: It is still controversial whether unilateral testicular torsion (TT) affects contralateral testis. The authors wanted to evaluate contralateral testicular damage in a rat model by the serum inhibin B levels, which is suggested as a marker of Sertoli cell function and spermatogenesis. METHODS: Fifty peripubertal male Wistar Albino rats were divided into 5 groups each containing 10 rats. Surgery was conducted under intraperitoneal 1-shot ketamine (50 mg/kg) anesthesia. Torsion-detorsion, torsion-detorsion-orchiectomies, orchiectomies, and sham operations were performed on the right testicle through a midline incision. Torsions were created by rotating the right testes 720 degrees in a clockwise direction and maintained by fixing the testes to the scrotum with a silk suture. Torsion duration was 4 hours. After each surgical intervention the incisions were closed. In group 1, 3-mL blood samples were taken to determine basal values of inhibin B in serum, and bilateral orchiectomies were performed. In group 2, 4 hours of torsion and detorsion was created and 1 month later, 3-mL blood samples were taken, and bilateral orchiectomies were performed. In group 3, 4 hours of torsion-4 hours of detorsion was created, and right orchiectomies were performed and 1 month later, 3-mL blood samples were taken and contralateral orchiectomies were added. In group 4, unilateral orchiectomies were performed, and 1 month later, 3-mL blood samples were taken, and contralateral orchiectomies were added. After the measurement of the serum inhibin B levels and histopathologic examinations, results are expressed as mean +/- SD. RESULTS: Serum inhibin B levels expressed as mean +/- SD were 108.233 +/- 21.296 pg/mL for group 1, 54.065 +/- 16.910 pg/mL for group 2, 74.195 +/- 2.779 pg/mL for group 3, 108.335 +/- 26.078 pg/mL for group 4, and 107.645 +/- 4.705 pg/mL for group 5. Inhibin B levels in group 2 and group 3 were different from group 1, group 4, and group 5 (P <.05). In histologic examination, Johnsen's scores expressed as mean +/- SD of right testes were 9.74 +/- 0.08 for group 1, 3.64 +/- 3.36 for group 2, and 9.86 +/- 0.05 for group 5. Histologic findings in group 2 were different from group 1 and group 5 (P <.05). Johnsen's scores expressed as mean +/- SD of left testes were 9.78 +/- 0.09 for group 1, 9.75 +/- 0.14 for group 2, 9.76 +/- 0.15 for group 3, 9.79 +/- 0.07 for group 4, and 9.82 +/- 0.08 for group 5, and there was no difference between groups (P >.05). CONCLUSIONS: The serum inhibin B levels decrease after unilateral TT reflecting contralateral testicular damage. Orchiectomy to prevent contralateral testicular damage after TT may not be effective after critical period. Measurement of inhibin B levels to evaluate contralateral testicular damage after unilateral TT is more effective than histopathologic examination.     

Prepubertal testicular torsion: subsequent fertility

Eighteen patients were reviewed 7 to 23 years after prolonged unilateral testicular torsion. They had all undergone surgical untwisting with replacement of the nonviable testis in the scrotum during prepubertal period. Five patients were now married and had fathered one or more children. Thirteen patients were unmarried. There was absence of testis on the affected side in 14 of 18 patients. Four patients had severe testicular atrophy on the affected side (testicular volume less than 1 mL). The contralateral side showed either a normal testicular volume or a compensatory hypertrophy (testicular volume greater than 25 mL). Seminal analysis was done in 13 unmarried men and it was completely normal in 10 patients. Two patients had low sperm density but normal semen volume and motility. One patient had pathologic semen analysis. IgG and IgA specific mixed agglutination reaction (MAR) test did not show evidence of sperm autoantibodies in any patient. Our clinical experience shows that, after prepubertal torsion, the contralateral testis undergoes normal development. Furthermore, torsion in the prepubertal male does not cause autosensitization and diminished fertility in adult life.     

大鼠一侧睾丸扭转对侧睾丸改变的实验研究

目的 :研究一侧睾丸扭转 (UTT)后对侧睾丸组织学及生精细胞凋亡的改变 ,以明确UTT后对侧睾丸是否存在损伤。　方法 :SD雄性大鼠 6 0只 ,随机分为实验组 (n =4 8)及对照组 (n =12 )。实验组采用Turner方法建立左侧睾丸扭转模型 ,于扭转后 6h处死 4只 ,其余 4 4只再分为扭转睾丸复位及切除组 ,分别于术后 1d、1周、4周处死7～ 8只 ,取睾丸组织进行组织学及生精细胞凋亡的检测。　结果 :UTT复位后对侧睾丸组织学发生明显改变 ,生精细胞凋亡指数明显高于对照组 (P <0 .0 5 )。扭转睾丸切除后对侧睾丸变化不明显。　结论 :UTT可引起对侧睾丸损伤 ,其机制可能与再灌注有关 ,扭转睾丸切除可防止或减轻对侧睾丸的损伤     

Serum inhibin B levels reflect contralateral testicular damage following unilateral testicular trauma

INTRODUCTION: The aim of this study was to evaluate contralateral testicular damage (CTD) following unilateral blunt testicular trauma (BTT) and testicular capsule laceration (TCL) by the serum inhibin B level which is an accepted marker of spermatogenesis. METHODS: Fifty peripubertal male Wistar albino rats were divided into 5 groups each containing 10 rats. Group 1 was the control group. Group 2 was the BTT group in which the right testicle was placed on a firm surface and a metal rod weighing 215 g was dropped onto the testicle from a height of 5.5 cm. Group 3 was the TCL group in which right testicular tunica albuginea was lacerated using the needle of 4/0 silk suture. Group 4 had right orchiectomy initially. Group 5 was the sham group. In all groups, 3-ml blood samples were taken and bilateral orchiectomies were performed 6 weeks after initial manipulations. RESULTS: Groups 2 and 3 had decreased inhibin B levels (p < 0.001), although the orchiectomy group had normal levels. Histological analyses showed lower Johnsen scores for both trauma groups in the ipsilateral and contralateral testes (p < 0.05). CONCLUSIONS: Serum inhibin B levels decrease following unilateral testicular trauma reflecting CTD.     

Flow cytometric DNA analysis demonstrates contralateral testicular deterioration in experimental unilateral testicular torsion of prepubertal rats

Summary. It has been postulated that unilateral testicular torsion causes damage to the contralateral testis and reduces fertility. However, in animal studies such an effect has not been fully proven by histopathologic examination or other conventional assays of spermatogenesis. We investigated the effect of unilateral testicular torsion on contralateral spermatogenesis in prepubertal rats using quantitative flow cytometric DNA analysis. Male rats were divided into three groups which underwent sham-operation, simple hemiorchiectomy or unilateral testicular torsion. Five weeks after these operations, fertility and spermatogenesis by flow cytometry were evaluated. No significant differences were observed in body weight, contralateral testicular weight or serum testosterone concentration among the three experimental groups. In the torsion group, mean seminiferous tubular diameter, number of foetuses, fertility rate and percentage of haploid cells were all significantly decreased compared to the other two groups. These results suggest that unilateral testicular torsion causes damage to the contralateral testis and consequently can reduce the future fertility of prepubertal rats.