- Email: [email protected]
Effect of Human Chorionic Gonadotropin Before Spermatic Vessel Ligation in the Prepubertal Rat Testis
Vol. 154,738-740,August 1995 Printed ln U S A .
EFFECT OF HUMAN CHORIONIC GONADOTROPIN BEFORE SPERMATIC VESSEL LIGATION IN THE PREPUBERTAL RAT TESTIS DAVID A. LEVY, FAD1 W. ABDUGKARIM, FLORO MIRALDI
AND
JACK S. ELDER
From the Departments of Urology, Pathology and Nuclear Medicine, Case Western Reserve University School
of
Medicine, Cleveland, Ohio
ABSTRACT
After single stage Fowler-Stephens orchiopexy testicular atrophy is common. Previous experimental study in the scrotal testis of the adult rat has shown that ligation of the internal spermatic artery often causes focal testicular infarction or atrophy and exogenous human chorionic gonadotropin increases testicular blood flow. We questioned whether division of the internal spermatic artery in the undescended r a t testis would also cause testicular injury and hypothesized that these changes might be prevented by administering human chorionic gonadotropin before vessel ligation. Two groups of 20-day-old Sprague-Dawley male rats were subjected to unilateral internal spermatic artery ligation. Group 1 (control) received no human chorionic gonadotropin, while group 2 received 10 IU human chorionic gonadotropin daily from days 3 to 17 of life. At 3 months testicular blood flow was quantitated using 141ceriumradioactive microspheres. The results indicated that blood flow on the operated side was lower t h a n on the nonoperated side but the change was not statistically significant. Human chorionic gonadotropin had no effect on blood flow to the operated testes. Gross testicular weights of operated versus nonoperated gonads were similar in rats that did and did not receive human chorionic gonadotropin. Pathological evaluation revealed normal histology in all testes. These results do not support the use of human chorionic gonadotropin preoperatively to stimulate collateral testicular blood flow. KEYWORDS:testis; gonadotropins, chorionic; rats, inbred strains Approximately 1%of male infants have an undescended age 20 days the male rats underwent right internal spertestis and undergo orchiopexy.1 As many as 20% of unde- matic vessel ligation under inhalational ether anesthesia. scended testes are nonpalpable of which many are intraA midline transabdominal incision was made and the right abdominal.2 In many boys with an intra-abdominal testis the colon was mobilized. Using a dissecting microscope the testicular artery and vein must be divided (Fowler-Stephens right ureter was identified at the right renal hilum, and orchiopexy) to allow placement of the testis in the ~ c r o t u m . ~ .the ~ right internal spermatic vessels were identified and liAfter Fowler-Stephens orchiopexy viability of the testis de- gated with a 6-zero silk ligature (operated testis). The right pends primarily on collateral circulation through the defer- colon was then returned to its normal anatomical position. ential artery and testicular atrophy occurs in approximately The left ureter was also exposed in each rat (nonoperated 20 to 50% of gonads subjected to this procedure.5-9 The ob- testis). The animals were allowed to wean and had free sewed postoperative changes in these gonads have been at- access to food and water during the next 2 months. Eventutributed to an inadequate or injured collateral blood supply. ally they were separated and housed 2 animals per cage. Clinical success With %stage Fowler-Stephens orchiopexy is At age 3 months the experimental animals were anesthesuperior to the 1-stage procedure, presumably because of tized with 50 mg./kg. sodium pentanembutol intraperidisruption or vasospasm of delicate collateral vessels in the toneally. The left inguinal fossa and hemithorax were shaved 1- stage procedue.'O and prepared with povidone-iodine scrub. A left inguinal In the postpubertal rat with scrotal testes division of the incision was made and the left femoral artery was cannuspermatic vessels has been reported to cause varying degrees lated with a 0.58 mm. internal diameter polyethylene cathof testicular atrophy.l*.12In this animal model ligation of the eter, which was secured with a 6-zero silk ligature. Through spermatic vessels initially causes a significant decrease in the femoral catheter each animal received 200 units hepatesticular blood flow but it ultimately returns to normal.13 rinized saline solution using a 5 cc syringe and 23 gauge Human chorionic gonadotropin has been reported to cause a needle. The muscles of the left chest were exposed and dissignificant increase in testicular blood flow in the mature sected off the rib cage, affording access to the ribs and interrat.14 We questioned whether ligating the testicular artery of costal muscles. The femoral arterial line w a s connected to a an undescended testis in the prepubertal rat would cause Harvard pump set a t a constant withdrawal rate of 0.3 cc per testicular injury and whether any changes could be pre- minute. Simultaneously, the Harvard pump was turned on vented by administering human chorionic gonadotropin be- and left thoracotomy was performed. Following vortex mixfore operative manipulation. ing of '*'cerium ( '*Ice) microspheres the appropriate volume containing 7 KCi. was drawn up into a 0.5 cc syringe using a MATERIALS A N D METHODS 27 gauge needle. The solution was then injected into the left A total of 20, 3-day-old Sprague Dawley male rats was atrium (10 rats) or left ventricle (10 rats). Blood from the housed 10 animals per cage with a lactating female rat. The syringe in the Harvard Pump w a s transferred to a carrier in female rat in each cage had free access to food and water. The which radioactivity could be counted by a gamma well juvenile male rats were randomly divided into 2 groups of 10 counter. The syringes were successively washed with a saline animals each. Group 1 served as a control while group 2 solution that was counted until the level of radioactivity in received daily subcutaneous injections of 10 IU human cho- the washing was equal to a previously determined backrionic gonadotropin for 14 days beginning on day 3 of life. At ground level of activity. 738
739
HUMAN CHORIONIC GONADOTROPIN BEFORE SPERMATIC VESSEL LIGATION
The left and right testicles were removed from each animal via a transcrotal approach and the perigonadal tissues, including the epididymis, were removed, leaving only the tunica albuginea and its contents. The gonads were then placed into test tubes of known weight and gonadal radioactivity was recorded, as was the wet weight of each gonad. Based on the measured radioactivity from the blood and testicles as well as the weight of the testicles, quantitation of testicular blood flow was calculated according to the following formulas: Total blood counts corrected Weight of withdrawn volume of blood = Counts per ml. per minute Time of blood withdrawal, Flow (ml. per minute) =
Tissue counts Counts per ml. per minute
Flow/gm. (testis)=
and
Flow Wet tissue weight.
Mean values for testicular blood flow in ml. per minute were calculated for the operated and nonoperated gonads in human chorionic gonadotropin treated and control animals. In addition, testicular blood flow in ml./gm. testis was calculated for all testes. Statistical analysis was performed using the 2-tailed Student t test. The testes were fixed in B o d s solution, embedded in paraffin, and stained with hematoxylin and eosin. At least 4 sections fmm each testis were examined by a single pathologist without knowledge of the treatment group. RESULTS
All animals survived the operative procedure performed at age 20 days. At 3 months technical problems precluded satisfactory assessment of testicular blood flow in 3 rats undergoing atrial injection of 141Ce (1 in the human chorionic gonadotropin and 2 in the no human chorionic gonadotropin group) and 1rat undergoing ventricular injection (no human chorionic gonadotropin group). The results of blood flow studies are shown in the table. Testicular blood flow was lower in gonads subjected to spermatic vessel ligation compared to nonoperated testes but this difference was not statistically significant (p = 0.11 in the no human chorionic gonadotropin and p = 0.22 in the human chorionic gonadotropin group). There was no demonstrable improvement in testicular blood flow in testes that had been exposed to human chorionic gonadotropin compared to the control. Testicular wet weights were similar in all animals. All histological sections examined had normal findings except that the microspheres could be seen in the testicular microcirculation. There were no discernible differences between any of the slides examined. Specifically, the parenchyma-tostroma ratio was normal. There was no evidence of edema, fibrosis, Leydig cell hyperplasia or inflammation in any of the sections. There was also no difference in the amount of spermatogenesis and presence of Sertoli cells. No infarcts or areas of necrosis were noted in any of the sections.
DISCUSSION
Approximately 8%of cryptorchid testes are intra-abdominal.16 Division of the internal spermatic vessels is often necessary to gain sufficient mobilization of the gonad to allow scrotal fixation.4 f i r Fowler-Stephens orchiopexy the testis must survive on collateral flow through the deferential artery. Previously, Pascual et a1 demonstrated that in adult rats with scrotal testes division of the internal spermatic artery caused an immediate 80%decrease in testicular blood flow but flow returned to pretreatment levels by 30 days after ligation.13 Geesaman et a1 showed that the administration of human chorionic gonadotropin to adult rats every other day caused testicular blood flow nearly to double immediately following the final injection.14 We theorized that division of the internal spermatic artery in the prepubertal undescended rat testis would result in testicular injury with concomitant decrease in blood flow to the testis. We also hypothesized that administering human chorionic gonadotropin for 2 weeks before ligation might protect the testis from ischemic damage by increasing collateral blood flow. Our results indicated that at age 20 days (the age of operative manipulation) division of the testicular artery caused a decrease in testicular blood flow but the change was not statistically significant. The administration of human chorionic gonadotropin before internal spermatic artery ligation had no demonstrable effect on the parameters measured. Furthermore, the testes had normal weight and morphology when examined 2 months later. These findings are different from those of others. For example, Ortolano and Nasrallah reported that spermatic artery ligation in adult rats resulted in a 34% decrease in testicular size and in 35-day-old (immature) rats it resulted in a 66% decrease in testicular size.11 Furthermore, 80% of the testes manifested various elements of infarction.11 Kelly et al reported that spermatic vessel ligation resulted in testicular sizes that were 6 to 21% of controls.12 Pascual et al found that, although the testicular weights of adult rats were not affected by spermatic vessel ligation, 83% had a variable number of necrotic tubules.13 Salman and Fonkalsrud reported similar histological changes in 3-month-old Wistar rats subjected to spermatic vessel ligation.16 Because the abnormal testicular changes in these studies were more significant in immature than mature rats, we predicted that at age 20 days (just before testicular descent) most testes subjected to spermatic vessel ligation would fail to develop normally. Furthermore, we thought that studying the effect of internal spermatic vein ligation before spontaneous testicular descent would be more relevant to the clinical application of Fowler-Stephens orchiopexy in the human, rather than investigating the effects on descended testes, as reported by others. However, all testes were normal in size and had normal histology. P a s 4 et al performed spermatic vessel ligation in 10-day-old rats and found that testicular blood flow at 60 days was 82% of controls (p <0.02), which is a result similar to ours with the exception that our study did not achieve statistical significance.l' The difference between our histological results and those of others is difficult to explain. Kelly et al performed spermatic vessel ligation in the inguinal canal.12 The testes in their
Efiect of human chorionic gonadotropin and ligation of the testicular artery in the prepubertal m t Operated Testes
Human Chorionic Gonadotropin (9 rats)
0.09682 0.023 Mean blood flow (mllmin.) 0.049 -c 0.012 Mean blood flow (mllgm.) 1.927 2 0.068 Testicular wt. (gm.) P value was not statietically significant.
No Human Chorionic Gonadotropin (7 rats) 0.0966 2 0.017 0.051 -C_ 0.008 1.893 lr 0.082
Nonoperated Testes Gonadotropin (9 rats)
No Human Chorionic Gonadohpin (7 rats)
c 0.004 0.066-C 0.013 1.915 2 0.064
0.147 2 0.002 0.081 2 0.017 1.892 t 0.080
Human Chorionic 0.128
740
HUMAN CHORIONIC GONADOTROPIN BEFORE SPERMATIC VESSEL LIGATION
study were quite small and fertility was 0%. It is conceivable that the collateral blood supply was impaired during operative manipulation. In other studies spermatic vase1 ligation was performed in the retroperitoneum, wing a technique similar to o m . The primary difference wae the age at which ligation was performed. Our resulta suggest that in the prepubertal rat collateral testidar blood flow may be better developed than in older rata and, therefore, the 20-day-old rat testis is protected from infarction after interruption of the main testidar blood supply. In developing an animal model that has potential application to the clinical use of Fowlerstephens orchiopeq study of the immature rat testis theoretically is more applicable than that of the adult Scrotal testis. The ideal model would include Fowler-Stephens orchiopexy of the undescended testis. Until such studies are performed, preoperative treatment with human chononic gonadotropin in children with an intra-abdominal testis for the purpoee of improving the outcome of single stage FowlerStephens orchiopexy does not seem warranted.
Ms. AM Robineon provided technical assistance. REFERENCES
1. Elder, J. S.: The d e s c e n d e d testis. Hormonal and aurgid management. Surg. Clin. N. Amer., 6fk 983,1988. 2. Elder, J. S.: Laparoecopy for impalpable testee:significance of the patent prummm vaginalie. J. Urol., part 2,16% 776,1994. 8. Fowler, R and Stephens, F. D.: The role of tee&icular vmcular anatomy in the aalvage of high undescended tegtes.Aust. New Zeal. J. Surg.. d !% 92,1959. 4. Elder, J. S.:Laparoecopy and FowlerStephens orchiopexy in the management of the impalpable testia. Urol. Clin. N. Amer., lS: 399,1989. 5. King, L. R: Optimal treatment of children with undexended taetee. J. Urol., 13s:734.1984.
6. Belker, A. M.: Urologic micmmrgwy-current
perspectives: 11. Orchiopexy and teaticular homotransplantation. Urology, 11: 103,1980. 7. Clatworthy. H. W., Jr., Hdenbaugh, R. S.and Grosfeld, J. L.: The gong-loop w''orchiopexyfor the high undeacendedtestis. Amer. Surg., s8: 69,1972. 8. Levitt. S. B., Kogan,S.J., Engel, R. M., W e b , R. M., Martin, D. C. and Ehrlich, R M.: The impalpable testis: a rational approach to management. J. Urol., 120:515,1978. 9. Hazebroek, F. W. J. and Molenaar, J. C.: The management of the impalpable testis by surgery alone. J. Urol., part 2,148:629, 1992. 10. Elder, J. S.:'ho-stage Fowler-Stephens orchiopexy in the management of intra-abdominal te8teS. J. Urol., 148:1239,1992. 11. Ortolano, V. and N d a h , P. F.: Spermatic vessel ligation (Fowler-Stephens maneuver): experimental results with regard to fertility. J. Urol., part 2,138:211, 1986. 12. Kelly, R. E.,Jr., Phillips, J. D., Fonkalerud, E. W. and Dinder, H.:Fertility after simulated Fowler-Stephens orchiopexy in rats. h e r . J. Surg., 16% 270,1992. 13. Pascual, J. A,Viiueva-Meyer, J., Salido, E., Ehrlich, R. M., Mena, I. and Rajfer, J.: Recovery of testicular blood flow following ligation of teaticular vessels. J. Urol., part 2,142:549, 1989. 14. Geeaaman, B., Viianueva-Meyer, J., Bluestein, D., Miller, L., Mena, I. and Rajfer, J.: Effecta of multiple isjections of HCG on testis blood flow. Urology, 40:81,1992. 15. Mod, J. W. and Belman,A. B.: A review of surgid treatment d undescended testes with emphaais on anatomical position. J. Urol., 140:125,1988. 16. Salman, F. T. and Fonhalerud, E. W.:Effecta of spermatic v a s cular division for correction of the high undescended testis on testicular function. Amer. J. Surg., 160: 506,1990. 17. P A , J. A,Viianueva-Meyer, J., Rutgers, J. L., L e d , C. A. E., Sikka, S.C., Ehrlich, R.M., Mena, I. and Rajfer, J.: Longterm effects of prepubertal testicular vessel ligation on testicular function in the rat. J. Urol., part 2,144.466,1990.
EFFECT OF HUMAN CHORIONIC GONADOTROPIN BEFORE SPERMATIC VESSEL LIGATION IN THE PREPUBERTAL RAT TESTIS DAVID A. LEVY, FAD1 W. ABDUGKARIM, FLORO MIRALDI
AND
JACK S. ELDER
From the Departments of Urology, Pathology and Nuclear Medicine, Case Western Reserve University School
of
Medicine, Cleveland, Ohio
ABSTRACT
After single stage Fowler-Stephens orchiopexy testicular atrophy is common. Previous experimental study in the scrotal testis of the adult rat has shown that ligation of the internal spermatic artery often causes focal testicular infarction or atrophy and exogenous human chorionic gonadotropin increases testicular blood flow. We questioned whether division of the internal spermatic artery in the undescended r a t testis would also cause testicular injury and hypothesized that these changes might be prevented by administering human chorionic gonadotropin before vessel ligation. Two groups of 20-day-old Sprague-Dawley male rats were subjected to unilateral internal spermatic artery ligation. Group 1 (control) received no human chorionic gonadotropin, while group 2 received 10 IU human chorionic gonadotropin daily from days 3 to 17 of life. At 3 months testicular blood flow was quantitated using 141ceriumradioactive microspheres. The results indicated that blood flow on the operated side was lower t h a n on the nonoperated side but the change was not statistically significant. Human chorionic gonadotropin had no effect on blood flow to the operated testes. Gross testicular weights of operated versus nonoperated gonads were similar in rats that did and did not receive human chorionic gonadotropin. Pathological evaluation revealed normal histology in all testes. These results do not support the use of human chorionic gonadotropin preoperatively to stimulate collateral testicular blood flow. KEYWORDS:testis; gonadotropins, chorionic; rats, inbred strains Approximately 1%of male infants have an undescended age 20 days the male rats underwent right internal spertestis and undergo orchiopexy.1 As many as 20% of unde- matic vessel ligation under inhalational ether anesthesia. scended testes are nonpalpable of which many are intraA midline transabdominal incision was made and the right abdominal.2 In many boys with an intra-abdominal testis the colon was mobilized. Using a dissecting microscope the testicular artery and vein must be divided (Fowler-Stephens right ureter was identified at the right renal hilum, and orchiopexy) to allow placement of the testis in the ~ c r o t u m . ~ .the ~ right internal spermatic vessels were identified and liAfter Fowler-Stephens orchiopexy viability of the testis de- gated with a 6-zero silk ligature (operated testis). The right pends primarily on collateral circulation through the defer- colon was then returned to its normal anatomical position. ential artery and testicular atrophy occurs in approximately The left ureter was also exposed in each rat (nonoperated 20 to 50% of gonads subjected to this procedure.5-9 The ob- testis). The animals were allowed to wean and had free sewed postoperative changes in these gonads have been at- access to food and water during the next 2 months. Eventutributed to an inadequate or injured collateral blood supply. ally they were separated and housed 2 animals per cage. Clinical success With %stage Fowler-Stephens orchiopexy is At age 3 months the experimental animals were anesthesuperior to the 1-stage procedure, presumably because of tized with 50 mg./kg. sodium pentanembutol intraperidisruption or vasospasm of delicate collateral vessels in the toneally. The left inguinal fossa and hemithorax were shaved 1- stage procedue.'O and prepared with povidone-iodine scrub. A left inguinal In the postpubertal rat with scrotal testes division of the incision was made and the left femoral artery was cannuspermatic vessels has been reported to cause varying degrees lated with a 0.58 mm. internal diameter polyethylene cathof testicular atrophy.l*.12In this animal model ligation of the eter, which was secured with a 6-zero silk ligature. Through spermatic vessels initially causes a significant decrease in the femoral catheter each animal received 200 units hepatesticular blood flow but it ultimately returns to normal.13 rinized saline solution using a 5 cc syringe and 23 gauge Human chorionic gonadotropin has been reported to cause a needle. The muscles of the left chest were exposed and dissignificant increase in testicular blood flow in the mature sected off the rib cage, affording access to the ribs and interrat.14 We questioned whether ligating the testicular artery of costal muscles. The femoral arterial line w a s connected to a an undescended testis in the prepubertal rat would cause Harvard pump set a t a constant withdrawal rate of 0.3 cc per testicular injury and whether any changes could be pre- minute. Simultaneously, the Harvard pump was turned on vented by administering human chorionic gonadotropin be- and left thoracotomy was performed. Following vortex mixfore operative manipulation. ing of '*'cerium ( '*Ice) microspheres the appropriate volume containing 7 KCi. was drawn up into a 0.5 cc syringe using a MATERIALS A N D METHODS 27 gauge needle. The solution was then injected into the left A total of 20, 3-day-old Sprague Dawley male rats was atrium (10 rats) or left ventricle (10 rats). Blood from the housed 10 animals per cage with a lactating female rat. The syringe in the Harvard Pump w a s transferred to a carrier in female rat in each cage had free access to food and water. The which radioactivity could be counted by a gamma well juvenile male rats were randomly divided into 2 groups of 10 counter. The syringes were successively washed with a saline animals each. Group 1 served as a control while group 2 solution that was counted until the level of radioactivity in received daily subcutaneous injections of 10 IU human cho- the washing was equal to a previously determined backrionic gonadotropin for 14 days beginning on day 3 of life. At ground level of activity. 738
739
HUMAN CHORIONIC GONADOTROPIN BEFORE SPERMATIC VESSEL LIGATION
The left and right testicles were removed from each animal via a transcrotal approach and the perigonadal tissues, including the epididymis, were removed, leaving only the tunica albuginea and its contents. The gonads were then placed into test tubes of known weight and gonadal radioactivity was recorded, as was the wet weight of each gonad. Based on the measured radioactivity from the blood and testicles as well as the weight of the testicles, quantitation of testicular blood flow was calculated according to the following formulas: Total blood counts corrected Weight of withdrawn volume of blood = Counts per ml. per minute Time of blood withdrawal, Flow (ml. per minute) =
Tissue counts Counts per ml. per minute
Flow/gm. (testis)=
and
Flow Wet tissue weight.
Mean values for testicular blood flow in ml. per minute were calculated for the operated and nonoperated gonads in human chorionic gonadotropin treated and control animals. In addition, testicular blood flow in ml./gm. testis was calculated for all testes. Statistical analysis was performed using the 2-tailed Student t test. The testes were fixed in B o d s solution, embedded in paraffin, and stained with hematoxylin and eosin. At least 4 sections fmm each testis were examined by a single pathologist without knowledge of the treatment group. RESULTS
All animals survived the operative procedure performed at age 20 days. At 3 months technical problems precluded satisfactory assessment of testicular blood flow in 3 rats undergoing atrial injection of 141Ce (1 in the human chorionic gonadotropin and 2 in the no human chorionic gonadotropin group) and 1rat undergoing ventricular injection (no human chorionic gonadotropin group). The results of blood flow studies are shown in the table. Testicular blood flow was lower in gonads subjected to spermatic vessel ligation compared to nonoperated testes but this difference was not statistically significant (p = 0.11 in the no human chorionic gonadotropin and p = 0.22 in the human chorionic gonadotropin group). There was no demonstrable improvement in testicular blood flow in testes that had been exposed to human chorionic gonadotropin compared to the control. Testicular wet weights were similar in all animals. All histological sections examined had normal findings except that the microspheres could be seen in the testicular microcirculation. There were no discernible differences between any of the slides examined. Specifically, the parenchyma-tostroma ratio was normal. There was no evidence of edema, fibrosis, Leydig cell hyperplasia or inflammation in any of the sections. There was also no difference in the amount of spermatogenesis and presence of Sertoli cells. No infarcts or areas of necrosis were noted in any of the sections.
DISCUSSION
Approximately 8%of cryptorchid testes are intra-abdominal.16 Division of the internal spermatic vessels is often necessary to gain sufficient mobilization of the gonad to allow scrotal fixation.4 f i r Fowler-Stephens orchiopexy the testis must survive on collateral flow through the deferential artery. Previously, Pascual et a1 demonstrated that in adult rats with scrotal testes division of the internal spermatic artery caused an immediate 80%decrease in testicular blood flow but flow returned to pretreatment levels by 30 days after ligation.13 Geesaman et a1 showed that the administration of human chorionic gonadotropin to adult rats every other day caused testicular blood flow nearly to double immediately following the final injection.14 We theorized that division of the internal spermatic artery in the prepubertal undescended rat testis would result in testicular injury with concomitant decrease in blood flow to the testis. We also hypothesized that administering human chorionic gonadotropin for 2 weeks before ligation might protect the testis from ischemic damage by increasing collateral blood flow. Our results indicated that at age 20 days (the age of operative manipulation) division of the testicular artery caused a decrease in testicular blood flow but the change was not statistically significant. The administration of human chorionic gonadotropin before internal spermatic artery ligation had no demonstrable effect on the parameters measured. Furthermore, the testes had normal weight and morphology when examined 2 months later. These findings are different from those of others. For example, Ortolano and Nasrallah reported that spermatic artery ligation in adult rats resulted in a 34% decrease in testicular size and in 35-day-old (immature) rats it resulted in a 66% decrease in testicular size.11 Furthermore, 80% of the testes manifested various elements of infarction.11 Kelly et al reported that spermatic vessel ligation resulted in testicular sizes that were 6 to 21% of controls.12 Pascual et al found that, although the testicular weights of adult rats were not affected by spermatic vessel ligation, 83% had a variable number of necrotic tubules.13 Salman and Fonkalsrud reported similar histological changes in 3-month-old Wistar rats subjected to spermatic vessel ligation.16 Because the abnormal testicular changes in these studies were more significant in immature than mature rats, we predicted that at age 20 days (just before testicular descent) most testes subjected to spermatic vessel ligation would fail to develop normally. Furthermore, we thought that studying the effect of internal spermatic vein ligation before spontaneous testicular descent would be more relevant to the clinical application of Fowler-Stephens orchiopexy in the human, rather than investigating the effects on descended testes, as reported by others. However, all testes were normal in size and had normal histology. P a s 4 et al performed spermatic vessel ligation in 10-day-old rats and found that testicular blood flow at 60 days was 82% of controls (p <0.02), which is a result similar to ours with the exception that our study did not achieve statistical significance.l' The difference between our histological results and those of others is difficult to explain. Kelly et al performed spermatic vessel ligation in the inguinal canal.12 The testes in their
Efiect of human chorionic gonadotropin and ligation of the testicular artery in the prepubertal m t Operated Testes
Human Chorionic Gonadotropin (9 rats)
0.09682 0.023 Mean blood flow (mllmin.) 0.049 -c 0.012 Mean blood flow (mllgm.) 1.927 2 0.068 Testicular wt. (gm.) P value was not statietically significant.
No Human Chorionic Gonadotropin (7 rats) 0.0966 2 0.017 0.051 -C_ 0.008 1.893 lr 0.082
Nonoperated Testes Gonadotropin (9 rats)
No Human Chorionic Gonadohpin (7 rats)
c 0.004 0.066-C 0.013 1.915 2 0.064
0.147 2 0.002 0.081 2 0.017 1.892 t 0.080
Human Chorionic 0.128
740
HUMAN CHORIONIC GONADOTROPIN BEFORE SPERMATIC VESSEL LIGATION
study were quite small and fertility was 0%. It is conceivable that the collateral blood supply was impaired during operative manipulation. In other studies spermatic vase1 ligation was performed in the retroperitoneum, wing a technique similar to o m . The primary difference wae the age at which ligation was performed. Our resulta suggest that in the prepubertal rat collateral testidar blood flow may be better developed than in older rata and, therefore, the 20-day-old rat testis is protected from infarction after interruption of the main testidar blood supply. In developing an animal model that has potential application to the clinical use of Fowlerstephens orchiopeq study of the immature rat testis theoretically is more applicable than that of the adult Scrotal testis. The ideal model would include Fowler-Stephens orchiopexy of the undescended testis. Until such studies are performed, preoperative treatment with human chononic gonadotropin in children with an intra-abdominal testis for the purpoee of improving the outcome of single stage FowlerStephens orchiopexy does not seem warranted.
Ms. AM Robineon provided technical assistance. REFERENCES
1. Elder, J. S.: The d e s c e n d e d testis. Hormonal and aurgid management. Surg. Clin. N. Amer., 6fk 983,1988. 2. Elder, J. S.: Laparoecopy for impalpable testee:significance of the patent prummm vaginalie. J. Urol., part 2,16% 776,1994. 8. Fowler, R and Stephens, F. D.: The role of tee&icular vmcular anatomy in the aalvage of high undescended tegtes.Aust. New Zeal. J. Surg.. d !% 92,1959. 4. Elder, J. S.:Laparoecopy and FowlerStephens orchiopexy in the management of the impalpable testia. Urol. Clin. N. Amer., lS: 399,1989. 5. King, L. R: Optimal treatment of children with undexended taetee. J. Urol., 13s:734.1984.
6. Belker, A. M.: Urologic micmmrgwy-current
perspectives: 11. Orchiopexy and teaticular homotransplantation. Urology, 11: 103,1980. 7. Clatworthy. H. W., Jr., Hdenbaugh, R. S.and Grosfeld, J. L.: The gong-loop w''orchiopexyfor the high undeacendedtestis. Amer. Surg., s8: 69,1972. 8. Levitt. S. B., Kogan,S.J., Engel, R. M., W e b , R. M., Martin, D. C. and Ehrlich, R M.: The impalpable testis: a rational approach to management. J. Urol., 120:515,1978. 9. Hazebroek, F. W. J. and Molenaar, J. C.: The management of the impalpable testis by surgery alone. J. Urol., part 2,148:629, 1992. 10. Elder, J. S.:'ho-stage Fowler-Stephens orchiopexy in the management of intra-abdominal te8teS. J. Urol., 148:1239,1992. 11. Ortolano, V. and N d a h , P. F.: Spermatic vessel ligation (Fowler-Stephens maneuver): experimental results with regard to fertility. J. Urol., part 2,138:211, 1986. 12. Kelly, R. E.,Jr., Phillips, J. D., Fonkalerud, E. W. and Dinder, H.:Fertility after simulated Fowler-Stephens orchiopexy in rats. h e r . J. Surg., 16% 270,1992. 13. Pascual, J. A,Viiueva-Meyer, J., Salido, E., Ehrlich, R. M., Mena, I. and Rajfer, J.: Recovery of testicular blood flow following ligation of teaticular vessels. J. Urol., part 2,142:549, 1989. 14. Geeaaman, B., Viianueva-Meyer, J., Bluestein, D., Miller, L., Mena, I. and Rajfer, J.: Effecta of multiple isjections of HCG on testis blood flow. Urology, 40:81,1992. 15. Mod, J. W. and Belman,A. B.: A review of surgid treatment d undescended testes with emphaais on anatomical position. J. Urol., 140:125,1988. 16. Salman, F. T. and Fonhalerud, E. W.:Effecta of spermatic v a s cular division for correction of the high undescended testis on testicular function. Amer. J. Surg., 160: 506,1990. 17. P A , J. A,Viianueva-Meyer, J., Rutgers, J. L., L e d , C. A. E., Sikka, S.C., Ehrlich, R.M., Mena, I. and Rajfer, J.: Longterm effects of prepubertal testicular vessel ligation on testicular function in the rat. J. Urol., part 2,144.466,1990.