Disturbance of Peripheral Microcirculation by LHRH-Agonists. II

It could be demonstrated with the aid of a cheek pouch model of the hamster that the LHRH-agonist lutrelin (Wyeth, WY 40972) caused disturbances of microcirculation within minutes, for example constriction of the arterioles and venules, reduction in capillary density and increased permeability, effects which were not reversible within the observation period (1 h) and could not be antagonized by the cyclooxygenase inhibitor indomethacin. Likewise, the lutrelin-induced accumulation of leucocytes in the capillaries of the testes of the rat could not be prevented within 6 hours after administration of indomethacin, whereas the harmful effect of lutrelin on the germinal epithelium could be antagonized by indomethacin within 24 hours. A biphasal course is assumed, characterised by an acute non-prostaglandin-dependent phase and a second prostaglandin-dependent phase, which causes the definitive damage to the testis of the rat.     

Effects of hypothermia on testicular ischemia

The ischemic effects of prolonged testicular torsion have been well documented; however, prevention or arrest of the damaging effects of prolonged ischemia has been incompletely studied. Two groups of Sprague-Dawley rats were subjected to varying lengths of bilateral testicular ischemia. Group I underwent normothermic ischemia for two, four, and six hours. Likewise, Group II underwent similar time periods of ischemia, however, after thirty minutes of normothermic ischemia the scrotum of each animal was placed into an ice bath maintained at 4C. Two weeks postoperatively, bilateral orchiectomy was performed. Histology of the testes of the two groups was compared. Neither group revealed significant destruction of the germinal epithelium after two hours of ischemia. Group I revealed only 25% preservation of the germinal epithelium at four hours and only 8% preservation at six hours of ischemia. In contrast, Group II which received ice showed 90% preservation of germinal epithelium at four hours and 85% preservation at six hours of ischemia. We conclude that external ice application significantly preserves seminiferous tubules at four and six hours of ischemic injury in the rat testicle.     

Acceleration of full-thickness wound healing in normal rats by the synthetic thrombin peptide, TP508

Thrombin is an essential factor in hemostasis, inflammation, and tissue repair. The synthetic thrombin peptide, TP508, binds to high-affinity thrombin receptors and mimics cellular effects of thrombin at sites of tissue injury. Treatment of full-thickness excisional wounds in normal rats with a single topical application of 0.1 microg TP508 (14 pmol/cm2) reproducibly accelerates wound closure, yielding wounds that on average close 39% more than controls by day 7 (p < 0.001). Wounds treated with 1.0 microg TP508 are 35% and 43% (p < 0.001) smaller than controls on day 7 and 10, respectively. The early rate of closure is approximately 40% greater in TP508-treated than vehicle-treated wounds (20 versus 14 mm2/day) and remains higher through day 7. Breaking strength after closure is slightly greater (15-23%) in wounds treated with TP508 than with saline alone. Histologic comparisons show that TP508 enhances recruitment of inflammatory cells to the wound site within 24 hours post-injury. TP508 treatment also augments revascularization of injured tissue, as evidenced at day 7 by the larger size of functional vessels in the granulation tissue and by the directed development of blood vessels to wounds. These studies raise the possibility that TP508 may be clinically useful in management of open wounds.     

Unilateral testicular disease: effect on the contralateral testis (morphometric study)

Unilateral testicular disease has been reported to damage the contralateral testis. In order to find out whether this detrimental influence is permanent in nature or can be avoided by therapeutic measures, and furthermore to quantify the damage, the following experiments were performed. Seventy-five rats were classified into the following five groups: I) testicular torsion persisting for eight hours; II) ipsilateral semicastration after torsion persisting for eight hours; III) semicastration; IV) sham operation as control; V) immunosuppression with azathioprine after torsion persisting for eight hours. The contralateral testes were removed two months later and perfused with fixative via the testicular artery. Stereologic techniques were employed to obtain quantitative morphologic data. Serum hormone levels were determined. The volume density of the contralateral germinal epithelium was not decreased two months after torsion for eight hours, torsion following by semicastration or torsion followed by immunosuppression. The same was true of the total volume of germinal epithelium per rat testis. The hormone levels remained essentially unchanged.     

Morphologic effects of unilateral cryptorchidism on the contralateral descended testis

Unilateral cryptorchidism is frequently accompanied by infertility. Uncertainty exists as to whether the infertility is a genetic effect or is related to an autoimmune reaction to the elevated testis. The effects of unilateral cryptorchidism were evaluated in 50 mice by surgically elevating the left testicle of 21-day-old mice into the abdomen (AT). A sham operation was performed on the left testicle of 50 control mice (SHT). The temperature of the abdominal testes measured 2.5 degrees C higher than the scrotal testes. The testes were removed from both sides at 1, 2, 3, 4 and 6 weeks postoperation. After testicular weights were recorded, seminiferous tubule diameters were measured, and germinal epithelium maturity was graded histologically using a modified Johnson testicular biopsy score. Progressive abnormal changes were seen in the contralateral descended testicles of AT as compared to SHT. By 3 weeks, though testicular weight changes were similar, mean seminiferous tubule diameter was smaller (P less than .001), and the germinal epithelium was less mature (P less than .001). These changes persisted through the sixth week. By changing the physiologic environment of one testicle, we have induced alterations in the histologic appearance of the contralateral testicle during the period of normal maturation.     

Protective effects of vitamin E on sodium arsenite‐induced toxicity,testicular measurements and histopathological studies of testes in Teddy goat bucks

The objective of this study was to investigate the toxic effects of arsenic on testicular measurements and histology of adult Teddy goats bucks and to examine whether these toxic effects are scavenged by vitamin E. Twelve adult Teddy goat bucks were divided randomly into three groups, A, B and C. Group A was kept as control, the B was given sodium arsenite 5 mg/kg BW per day, and group C was fed with vitamin E 200 mg/kg BW per day + arsenic 5 mg/kg BW per day. This treatment was continued for 84 days. Analysis of data revealed that the testicular measurements (scrotal circumference, width, length and weight) were significantly reduced in arsenic‐treated animals, whereas there were ameliorating effects of vitamin E on these parameters. The major histopathological changes were present in the form of loss of germinal epithelium, atrophy of Leydig cells and vacuolations. Vitamin E in combination with sodium arsenite increased the active spermatogenesis as well as restoration of germinal epithelium. It can be concluded from the present findings that sodium arsenite causes toxicity in the male reproductive system of Teddy goat bucks with major changes in parenchyma of testes. Supplementation of vitamin E has protective effects on the toxicity of sodium arsenite on the reproductive system of male Teddy goat bucks.     

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.     

Stagnation of blood in the microvasculature of the affected and contralateral testes of men with short-term torsion of the spermatic cord

Bilateral testicular biopsies from four men with a short duration (3 hours 10 minutes to 4 hours 30 minutes) of unilateral spermatic cord torsion and testicular biopsies from six men with irreversible brain death were used for the present investigation. Extensive light and electron microscopic studies and quantitative analyses of all biopsy materials were performed. The torsioned testes revealed variable degrees of damage to the seminiferous tubules, including germ cell disorganization and sloughing of immature germ cells. Ninety-five percent of the blood vessels from the biopsied tissue specimens were clogged with blood cells. The seminiferous tubules of the contralateral testis had normal germ cell arrangements and counts. However, 88% of the microvessels from the tissue biopsied from the contralateral testes were packed with blood cells, whereas only 10% of the blood vessels in the control biopsy specimen were clogged with blood cells. At the electron microscopic level, fewer tight junctions and enlarged pores were found between the endothelial cells of the affected vessels, and microvilli were completely absent from these endothelial cells. The clogging caused by blood cells in the affected vessels was so severe that no space was found between the membrane of the endothelial cell and the membrane of the blood cells. It has been suggested that local clogging by blood is responsible for the initiation of degenerative changes in the testes of men with unilateral torsion of the spermatic cord.     

Morphological and histochemical effects of 2,3,7,8-tetrachlorodibenzo-p dioxin (TCDD) on marmoset (Callithrix jacchus) testes

The testes of marmosets (Callithrix jacchus), which had been treated with a single dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (0.3 microgram to 10 micrograms/l kg body weight (BW)) were studied after 7 days using morphological and histochemical techniques. Light microscopic and electron microscopic examination revealed decreased intercellular contact in the germinal epithelium, as indicated first by enlarged intercellular spaces between the Sertoli's cells and between the Sertoli's cells and neighboring germ cells (i.e., spermatogonia and preleptotene spermatocytes), particularly in the basic compartment of the germinal epithelium. Second, decreased intercellular contact was indicated by the accumulation of premature spermatids and spermatocytes in the tubular lumen after TCDD treatment. The Sertoli's cells exhibited an increased amount of lipids, phagolysosomes, and vacuoles in their cytoplasm. Spermatids were frequently affected by TCDD, particularly during early spermiogenesis. These alterations included vacuolization of the cytoplasm and the development of additional germinal vesicles. This special effect on spermiogenesis became even more evident quantitatively by determination and counting of tubular stages in semithin sections. Tubular determination on the basis of the appearance of spermatids revealed that the ratio of tubular stages I to III became lower and that of stages V to VII became higher, dose dependently, indicating a maturation stop at the beginning of spermiogenesis caused by TCDD treatment. After TCDD treatment, Leydig's cells were morphologically unaffected, but histochemical investigations revealed decreased activity of 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD). The sensitivity of the applied methods was different in view of the level of unaffection. The effect of Leydig's cells, as indicated by the decreased activity of 3 beta-HSD, had already been found at a dose of 1 microgram/kg BW TCDD, whereas clear-cut morphological and morphometrical effects were seen at 3 micrograms/kg BW for the first time. Moreover, with the special effect on spermiogenesis in marmoset monkeys, the findings demonstrate that the toxicity of TCDD on testicular morphology is species specific.     

Effect of normobaric hypoxia on the testis in a murine model

High‐altitude hypoxia generates spermiogram impairment due to germinal epithelium, Leydig cells, sperm and seminal plasma alterations, but precise mechanisms involved are unknown. The objective of this work was to analyse the effect of normobaric hypoxia on the morphology of testicular interstitium and some associated molecular and hormonal factors. Twenty‐four mice were exposed to normobaric hypoxia (8.1% inspired oxygen fraction) during 20 days. The effects on body weight, testicular weight, vascularisation, testosterone, HIF1‐α and VEGF were analysed at different periods of exposure and compared to controls. Hypoxic mice had lower body weight than mice kept in normoxia. Testicular weight raised significantly the 1st day, but remained normal during the rest of experiment. Number of blood vessels per field and mean diameter of vessels were higher in hypoxic mice. Plasmatic and testicular testosterone raised during first 24 h of hypoxia, but decreased on the 5th day. Vascular/interstitial ratio (proportion of interstice occupied by blood vessels) duplicated at the end of the experiment. Most substantial early effects of hypoxia were testicular oedema, increase in number and diameter of blood vessels and elevation of plasmatic and testicular testosterone. Normobaric hypoxia generates similar effects to those induced by hypobaric hypoxia.     

Structural and ultrastructural modifications of cryptorchid human testes

Structural and ultrastructural modifications have been studied in cryptorchid testes. Biopsies were obtained from 15 patients between 2 and 39 years old, including 7 who had been treated previously by hormonal therapy without success. The most considerable observations were 1) the precocity of damage in germinal epithelium and in peritubular connective tissue, 2) the presence of frequent bilateral damage in cases of unilateral cryptorchidism and 3) the inefficacy of hormonal treatment (human chorionic gonadotropin) on the delay in maturation of tubular epithelium. These findings offer further information about the optimal time for surgical treatment of cryptorchidism, which in our opinion should be done when the patient is less than 2 years old.     

Testicular function after local injection of 6-hydroxydopamine or norepinephrine in the golden hamster (Mesocricetus auratus)

Although there is evidence for the sympathetic innervation of the mammalian testis, the function of noradrenergic fibers is not understood. This in vivo and in vitro study in the adult golden hamster examines testicular function after unilateral intratesticular application of a single dose of 6-hydroxydopamine (6-OHDA), a neurotoxic drug known to produce depletion of noradrenergic stores in nerve endings. The contralateral testis in each animal was injected with vehicle alone and served as the control. After 24 h, the content of norepinephrine (NE) in testicular parenchyma was reduced in most testes injected with 6-OHDA. At this time, concentration of luteinizing hormone receptors (LH-R) was significantly decreased in the 6-OHDA treated testis, compared with the vehicle-injected testes. This decrease was followed by a significant increase at 72 h. The concentration of LH-R was not significantly altered 10, 48, 144, or 168 h after 6-OHDA administration. Changes in testicular testosterone (T) concentrations paralleled the changes in LH-R at most time points. In the incubations of control vehicle injected testes, addition of NE did not affect T production but stimulatory action of hCG was significantly augmented by concomitant exposure to NE at most time points after injection of vehicle. In incubations of 6-OHDA-injected testes, a comparable pattern of T responses to NE and hCG was found only 48 h after injection. At 24 h post injection NE alone significantly stimulated T production; at 10 and 24 h the ability of NE to potentiate the action of hCG was significantly reduced, while at 72 and 144 h basal T production and the stimulatory hCG effect were significantly increased. Moreover, at 72, 144, and 168 h, the effect of NE & hCG on T production was significantly greater in 6-OHDA-injected testes than in the vehicle injected testes of the same animals. In incubations of untreated hamster testes, addition of 6-OHDA at doses similar to those used for injections did not affect T production. Weights of 6-OHDA injected testes were slightly but significantly reduced after 144 and 168 h. These changes were most likely due to degenerative changes of the germinal epithelium, which were clearly detectable 168 h post injection. Because 6-OHDA can release NE from nerve terminals, the observed effects of 6-OHDA might have been initiated by supernormal testicular NE concentrations. To examine this possibility, the authors have tested the effects of intratesticular NE injections. This treatment caused decrease of LH-R at 24 h followed by an increase at 72 h.(ABSTRACT TRUNCATED AT 400 WORDS)     

离体睾丸缺血再灌注损伤的实验研究

目的 探讨人离体睾丸缺血再灌注损伤的变化规律。了解益生注射液对其变化的干预效果。方法 采用13人摆脱赠尸睾丸26只,用4℃250ml高渗枸橼酸盐嘌呤液冷保存,再以此液500ml再灌注,实验组用含500μg/ml益生注射液同法操作,同一睾丸于单纯冷保存（对照组睾丸8只,实验组8只）6、12、18、24、36、48、60和72小时连续取材,冷保存6、12、18、24和36小时（对照组与实验组每时间点各1只,共10只）后,37）复温再灌注6和12小时连续取材,作组织学及酶组织化学染色。结果 实验组睾丸组织4℃冷保存24小时内无明显病理改变;36和48小时后出现精索血管内皮细胞肿胀,变性及部分脱落,曲细精管与生精上皮剥离,间质轻度水肿等损伤;冷保存12小时乳酸脱氢酶与琥珀酸脱氢酶活性增高,24小时后又降低;一氧化氮合成酶活性于冷保存18小时后降低再灌注后组织损伤加重,对照组睾丸单纯冷保存12小时即出现精索血管内皮细胞肿胀,变性,24小时后加重,再灌注后精索血管大量内皮细胞变性脱落,曲细精管基膜剥离和间质水肿严重。结论 4℃冷保存24小时内仅有内皮细胞轻微损伤,超过24小时可引起睾丸血管及组织形态结构明显异常,37℃复温再灌注使损伤程度加重,益生注射液使人离体睾丸在4℃冷保存24小时内保持正常形态结构。且对再灌注损伤有保护作用。     

Effect of prolonged cryptorchidism on germ cell apoptosis and testicular sperm count

Aim:To evaluate the long term effect of experimental cryptorchidism on germ cell apoptotic rate and testicular sperm content in adult rats.Methods:Bilateral cryptorchidism was created in 40 adult male Sprague-Dawley rats by surgically manipulating the testes into the abdominal cavity and closing the internal inguinal ring.The rats were sacrificed and the testes removed 6 hours and 2,4,7,21,28 and 56 days after cryptorchidism.Germ cell apoptosis was quantified by means of TUNEL assay and apoptosis was confirmed using transmission electron microscopy.Results:The rate of apoptosis peaked at 4 days of cryptorchidism and then progressively declined to a nadir at 14 days of cryptorchidism.At 56 days of cryptorchidism,the germinal epithelium was largely depleted by the apoptotic process and only a few mature sperm were seen within the testis.At this point,a few tubules were seen to be repopulating with primary spermatocytes and the level of germ cell apoptosis began to increase marginally.Testicular sperm count (TSC) began to decline rapidly at day 7 of cryptorchidism.Only a few mature sperm were found in the testes of rats following 56 days of cryptorchidism.Multinucleated giant cells (MGC) were most numerous within the seminiferous tubules at day 4.At day 7,35% of MGCs were TUNEL positive.At all subsequent time points,however,MGCs fail to stain positive for apoptosis.This resumption of increased apoptosis coincided with the appearance of a population of primary spermatocytes in some seminiferous tubules.Moreover,there was not a corresponding increase in the number of mature sperm after 56 days of cryptorchidism.Conclusion:The decline in germ cell apoptosis after 4 days of cryptorchidism can be attributed to be the result of an overall depletion of germ cells.It appears that after a prolonged cryptorchidism (56 days),there is a limited resumption of spermatogenesis presumably as a result of a decrease in the maturing germ cells undergoing programmed cell death.(Asian JAndrol2004 Mar;6:47-51)     

The Anti-Reproductive Effects of Long Term Oral Administration of Cadmium on the Adult Male Rat

The toxic effects of prolonged oral administration of cadmium on gametogenic and endocrine function of testes of adult rats were investigated. The experimental animals received daily, for 3, 6, 12 or 15 months, pellets containing 8.8 mg or 88 mg of cadmium chloride per kg body weight.
The rats treated with the higher doses of cadmium for 12 and 15 months showed a marked reduction in absolute weight of testes accompanied by histological signs of impairment of seminiferous tubules. There were no necrotic changes but a number of cross-sections of seminiferous tubules were deprived of spermatocytes and spermatids, reaching about 50 per cent of the tubules in the rats treated with higher doses of cadmium. The appearance of histological changes in rats treated for 12 and 15 months correlated with cumulation step of cadmium in testes and with alterations in serum concentration of LH but not of testosterone. Therefore, we suppose that under these experimental conditions the impairment of seminiferous tubules was induced by the direct influence of cadmium on germinal epithelium beginning the moment when cadmium reaches an effectively toxic concentration in testis.     

Repeated interruptions of the testicular blood flow do not have long-term effects on spermatogenesis in the ram

Summary. The effect of repeated interruptions of the testicular blood flow on spermatogenesis was studied in mature Texel rams. Reversible interruption of the blood flow was achieved by an inflatable occluder, placed around the testicular artery at the level of the spermatic cord. In eight testes the blood flow was successfully interrupted six times for 1 h within 3 weeks and in 14 testes nine times for 1 h within 3 weeks. Nine weeks after the last blood flow interruption spermatogenesis was evaluated in histological sections of the testes. Both after six and nine blood flow interruptions a qualitatively complete epithelium was found in at least 90% of the seminiferous tubules. Cell counts in stages VII and VIII of the spermatogenic cycle revealed a slight decrease of spermatocytes and spermatids in the tubules with a complete epithelium after nine occlusions, which was only statistically significant for Preleptotene Spermatocytes. After six occlusions the numbers of all cell types were at or even slightly above control levels. These results show that repeated periods of ischaemia for 1 h do not result in conspicious long-term damage to spermatogenesis.     

Collateral circulation after spermatic vessel ligation for abdominal testis and its impact on staged laparoscopically assisted orchiopexy

PURPOSE: Staged laparoscopically assisted orchiopexy for abdominal testis entails initial spermatic vessels ligation followed by mobilization of the testis, preserving the vas and its vessels as a sole source of testicular blood supply. This mobilization includes all peritoneal attachments of the testis, including the gubernaculum, which may carry collateral circulation to the testis. This study considers the anatomy of the gubernaculum and the collateral circulation after spermatic vessels ligation and its possible effects on the viability of the testis. MATERIALS AND METHODS: The anatomy of the gubernaculum and the effect of spermatic vessels ligation on the collateral circulation were studied in 90 boys with 100 abdominal testes with a short pedicle. Patients with vanishing testis or those not needing ligation of the spermatic vessels were excluded from the study. The anatomy and the vascularity of the testis, gubernaculum, and vas were studied at initial laparoscopy and 6 weeks later after spermatic vessel ligation. Based on these findings, the technique for laparoscopically assisted orchiopexy were modified, preserving the gubernaculum whenever possible in cases having prominent collaterals. RESULTS: Based on the attachment and blood vessel configuration of the gubernaculum, the patients were divided into two groups: in group 1 (open internal ring), there were 46 testes in which the gubernaculum passed through an open internal ring having an inguinal attachment. In group 2 (closed internal ring), there were 54 testes with a soft gubernaculum attached to a closed internal ring without inguinal attachment. In group 1 the gubernaculum was short and tough in 32 of 46 testes, with no visible blood vessels in all cases. In group 2 the gubernaculum was long and soft in 43 of 54 testes and showing evident blood supply before clipping of the spermatic vessels in 30 testes. Subsequent laparoscopy done after 6 weeks showed prominent collateral circulation around the gubernaculum in 26 testes and around the vas in 20 testes in the group 1 patients, and around the vas in 20 and the gubernaculum in 34 testes in group 2. Preservation of the gubernaculum was possible in 43/54 (80%) of group 2 patients and in 14/46 (30%) of group 1 patients. CONCLUSION: Routine cutting of the gubernaculum is not necessary for proper mobilization of the abdominal testis: collateral circulation varies from patient to patient, and once the gubernaculum shows prominent blood supply, its preservation is mandatory. The decision to cut the gubernaculum should be taken while the performing initial spermatic vessel ligation and not during the second stage to avoid compromise of the settled collateral circulation.     

Effect of long‐term testosterone propionate or human chorionic gonadotrophin administration on reproductive glands in adult male rabbits

The study was aimed to investigate the effect of testosterone propionate (TP) or human chorionic gonadotrophin (hCG) treatment on reproductive glands in sexually mature male rabbits. A total 36 adult male rabbits were randomly distributed to six equal groups. The first control group (CON), the second treated with low‐dose TP (TPL), the third treated with high‐dose TP (TPH), the fourth treated with low‐dose hCG (CGL), the fifth treated with medium‐dose hCG (CGM) and sixth treated with high‐dose hCG (CGH). At the 16th post‐treatment week, the animals were sacrificed, and the testes and accessory sex glands dissected, weighted and stored at ?20 °C until assay. Testosterone propionate treatment in both doses resulted in reduction (P < 0.01) in testicular weight and increase (P < 0.01) in weight of vesicular gland, paraprostate and proprostate glands. High‐dose TP increased the weight of prostate and bulbouretheral gland (BUG). Testosterone propionate increased total androgen (P < 0.01) with Testosterone (T) predominating in serum, dihydrotestosterone (DHT) predominating in testes and most accessory sex glands. High dose of hCG increased the weight of proprostate and paraprostate glands. Androgen level in serum, testes and accessory sex glands increased (P < 0.01) after hCG treatment.     

Effects of simulated Fowler-Stephens orchiopexy on testicular structure and function in rats.

To determine the effects of the Fowler-Stephens orchiopexy (FSO) on testicular structure and function, young rats underwent simulated FSO and concurrent contralateral orchiectomy, unilateral orchiectomy, or no operation. Rats were killed at 1, 2, 4, 6, 8, and 10 weeks postoperation, and serum testosterone, as well as testicular concentrations of the enzymes LDH & SDH, protein markers of testicular germinal cell development, were measured at the time of death. Although LDH and SDH concentrations decreased by 45 per cent in testes after simulated FSO at 4 weeks, control testes showed a 5 per cent increase in these enzymes. Serum testosterone decreased to one-fourth the initial value in rats after FSO, whereas control rats showed a slight increase. Within 2 weeks after simulated FSO, spermatocytes and sperm were sparse and there was marked disruption of tubular morphology; after 4 weeks interstitial fibrosis became prominent. Only a rare testis with good collateral vessels and resultant good histologic appearance and enzyme profile survived the FSO procedure, and these testes were considerably smaller than the controls.     

Acute and long-term effects of a single dose of the fungicide carbendazim (methyl 2-benzimidazole carbamate) on the male reproductive system in the rat.

The effects of carbendazim (methyl 2-benzimidazole carbamate) on the testis, efferent ductules, and sperm were determined in the adult rat after a single oral dose. Two experimental trials were performed: a time response between 2 hours and 32 days after exposure using 0 and 400 mg/kg, and a dose response at 2 and 70 days after exposure using 0 to 800 mg/kg doses. In experiment 1, effects were seen throughout the 32-day period, beginning 8 hours after exposure; the effects included first an increase in testis weight, then decreases in testicular spermatid numbers and in the percentage of morphologically normal cauda sperm. In experiment 2, significant testicular and efferent ductal alterations occurred in animals treated with doses of 100 mg/kg or greater. A dose-dependent increase in testicular weight 2 days after treatment was accompanied by increases in seminiferous tubular diameter and excessive loss of immature germ cells in a stage-dependent manner. There was also a dose-dependent increased incidence of occlusions in the efferent ductules. The occluded ductules were characterized by severe inflammation and exhibited disorganization of the epithelium. At 70 days, there were dose-dependent decreases in mean testis weight and mean seminiferous tubular diameter; however, only minimal long-term effects were seen at 50 mg/kg. In testes exhibiting seminiferous tubular atrophy of greater than 25% (100 mg/kg or greater doses), all of the testes were associated with efferent ductules containing occlusions. Caput sperm numbers were significantly reduced in these testes. Occlusions, abnormal ductules, fibrosis, spermatic granulomas, and mineralization were observed in the ductuli efferents. Long-term effects of carbendazim on the testis were induced primarily by ductal occlusions. Results show that carbendazim produces more severe short- and long-term effects on the male reproductive system than the fungicide benomyl.