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Endocrinology Vol. 140, No. 3 1349-1355
Copyright © 1999 by The Endocrine Society

ARTICLES

The Detrimental Effects of Spinal Cord Injury on Spermatogenesis in the Rat Is Partially Reversed by Testosterone, but Enhanced by Follicle- Stimulating Hormone1

Hosea F. S. Huang, Ming-Tang Li, William Giglio, Robert Anesetti, John E. Ottenweller and Leonard M. Pogach

Veterans Affairs Medical Center (H.F.S.H., W.G., J.E.O., L.M.P.), East Orange, New Jersey 07019; and Department of Surgery, Section of Urology (H.F.S.H., M.-T.L.) and Neuroscience (J.E.O.) University of Medicine and Dentistry-New Jersey Medical School, Newark, New Jersey 07103


   Abstract
Top
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Our previous studies have demonstrated that impaired spermatogenesis during the acute phase of spinal cord injury (SCI) is preceded by a transient (but significant) suppression of serum FSH, LH, and testosterone (T) concentrations. It is hypothesized that hormonal deprivation may impair Sertoli cell function, leading to the loss of spermatogonia, degeneration of spermatogenic cells, and eventual regression of the seminiferous epithelium. The current study examined the efficacy of exogenous T and FSH in the maintenance of spermatogenesis and Sertoli cell functions in SCI rats.

Implantation of T capsules (TC, 2 x 5 cm) attenuated some of the spermatogenic lesions and maintained qualitatively complete spermatogenesis in all SCI rats 4 weeks after the surgery. In contrast, daily injections of 0.1 U of FSH alone, or in combination with TC implants, paradoxically enhanced the regression of spermatogenesis in SCI rats. At this time, the numbers of Aal, A1, and B spermatogonia and preleptotene spermatocytes in SCI rats have decreased by 25–30%. Though not prevented by TC implants, the decrease in Aal and A1 spermatogonia was attenuated by FSH alone but was further enhanced when FSH-treated rats also received TC implants. The intratesticular T concentration in untreated and FSH-treated SCI rats was not different from that of sham control rats, but it decreased by more than 95% in those SCI rats given TC implants alone. These results demonstrate that impairment of spermatogenesis during the acute phase of SCI is not related to the availability of FSH and/or T. Northern blot analysis revealed an increase in androgen receptor messenger RNA (mRNA) in the testis of SCI rats; this increase was prevented by TC implants but persisted when FSH was also given. In contrast, the levels of FSH-receptor, androgen binding protein, and transferrin mRNA were not affected by SCI but were significantly higher in those SCI rats given FSH alone or in combination with TC. TC implants alone suppressed mRNA levels of transferrin in testes of SCI rats, without concomitant change in those for FSH-receptor and ABP. The changes in Sertoli cell responses to FSH and T, and perhaps other hormones, may alter signal events elicited by these hormones, thus contributing to abnormal epithelial environments and regression of spermatogenesis. Maintenance of spermatogenesis in SCI rats by exogenous T suggests the feasibility of using exogenous hormones to impede the detrimental effects of SCI on spermatogenesis. This approach may have clinical applicability for the preservation of spermatogenic functions in SCI men.


   Introduction
Top
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
AFTER SPINAL CORD injury (SCI), fertility in men is generally impaired and is associated with abnormal semen qualities characterized by a decrease in sperm count and progressive motility, and an increase in sperm with abnormal morphology (1, 2, 3, 4). These observations suggest that multiple factors may contribute to the deterioration of sperm function after SCI. In surgically induced SCI rats, abnormalities in spermatogenesis are apparent within 1 week after SCI, and some of these lesions resemble those that occur after androgen deprivation (5, 6, 7). In addition, while spermatogonial proliferation persists, there is a decrease in the number of various types of spermatogonia and preleptotene spermatocytes within 4 weeks after SCI (8). These effects occur at the same time as transient (but significant) decreases in serum FSH and LH, as well as intratesticular testosterone (ITT) concentrations (5), suggesting that the lowered FSH and/or testosterone (T) may contribute to the early effects of SCI on spermatogenesis.

Spermatogenesis continues to deteriorate during the chronic phase of SCI, even after relatively normal function of the pituitary-testis hormone axis has been restored (8, 9). We have postulated that SCI may result in persisting Sertoli cell abnormalities that, in turn, may contribute to the regression of spermatogenesis during the chronic stage of SCI. It has been reported that T alone is sufficient to restore and maintain qualitatively complete spermatogenesis in hypophysectomized rats, and these effects can be facilitated by FSH (10, 11). The current study investigates the efficacy of these hormones in the maintenance of spermatogenesis in SCI rats and functional status of Sertoli cells.


   Materials and Methods
Top
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
Animals
Mature Sprague Dawley rats (300–350 g, Taconic Farms, Inc., Taconic, NY) were caged individually in an air-conditioned, light-controlled animal room for 2 weeks before the experiment. Animals were fed Purina rat chow (Ralston Purina, St. Louis, MO) and water ad libitum. Animals were assigned randomly to receive either SCI or sham operation. A total of 60 rats were subjected to surgically-induced SCI by procedures described previously (5, 9). Beginning immediately after surgery, the SCI rats were given daily injections of 0.1 U porcine FSH (Sigma Chemical Co., St. Louis, MO) for 14 days, sc implantation of 2 x 5 cm T capsules (TC) for the duration of the experiment, or a combination of both. Control animals received sham operations without hormone replacement. Animals were hemicastrated 4 weeks later under phenobarbitol anesthesia through a midscrotum incision. The animals were subsequently killed 8 weeks later by decapitation (12 weeks after SCI). The surgical procedures, including transection of spinal cord and hemicastration, have been approved by Institutional Animal Care and Use Committee of both the Veterans Affairs Medical Center and University of Medicine and Dentistry-New Jersey Medical School.

Half of each testis, obtained 4 weeks post SCI or post sham operation, was fixed in Bouin’s solution and processed for histology or whole mounts of the seminiferous tubules (6, 7). The normalcy of spermatogenesis and quantitative analysis of spermatogonial proliferation were evaluated as described previously (5, 6, 7). The remaining half of the testis was frozen immediately in isohexane, immersed in a mixture of methanol and dry ice, and stored at -80 C. The second testis from each rat, recovered at the end of the experiment, was fixed in Bouin’s solution and processed for histology.

Northern blot complementary DNA (cDNA) hybridization
The procedures for isolation of testicular RNA (12), purification of poly (A)+ RNA by oligo dT cellulose chromatography (13), electrophoresis, and Northern blotting of RNA (14) have been described previously (5, 15). The cDNA probes for FSH-receptor (FSH-R) (16), androgen receptor (AR) (17), androgen binding protein (ABP) (18), and transferrin (Trf) (19) were isolated by agarose electrophoresis after appropriate endonucleases digestion. These probes were radiolabeled with 32P-deoxycytidine triphosphate using a random priming kit (Boehringer Mannheim, Indianapolis, IN) and were used within 24 h for hybridization by the procedures described previously (5, 15). The autoradiographs were developed, after 1–6 days of exposure, using an intensifying screen. The membranes were subsequently stripped and rehybridized with 32P-labeled cDNA for 18S ribosomal RNA. The relative abundance of each messenger RNA (mRNA) transcript (FSH-R: 2.6 kb; AR: 9.4 kb; ABP: 1.7 kb; Trf: 2.7 kb; and hemiferrin: 0.9 kb) were estimated by densitometry and normalized against that of the 18S ribosomal RNA in each sample. The average ratio between the mRNA and the 18 S ribosomal RNA of the control animals in each blot was considered 100%, and the results for individual control and experimental samples in each blot were expressed as a percentage of this average.

Hormone measurement
ITT concentration was determined in ether extract of 50–100 mg testicular tissue, according to the procedures described previously (6, 7).

Statistics
All data were analyzed to determine that they were normally distributed. Subsequently, the organ weights were evaluated by 2 (time points) x 5 (treatment groups) ANOVA. The number of spermatogenic cells, ITT concentrations, and levels of Sertoli cell protein mRNAs were also analyzed by 1 x 4 ANOVA. When the treatment effects were significant (P < 0.05), Dunn’s tests were used to determine the significance of differences among treatment groups.


   Results
Top
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
Organ weights
Testis and epididymis weights were significantly reduced 4 weeks after SCI (P < 0.05, Table 1Go). Daily injection of FSH during the first 2 weeks after SCI resulted in an additional 10% decrease in testis weight, although not statistically significant. In contrast, implantation of 10 cm TC caused a significant decrease in testis weights in SCI rats (P < 0.05), and this decrease was enhanced by coadministration of FSH (P < 0.05). Twelve weeks after SCI, testis weights of 3 untreated SCI rats were 45% lower than that of sham-operated controls (P < 0.05) and were even lower in those SCI rats that had received FSH at the beginning of the experiment. TC implantation attenuated the decrease in testis weights of SCI rats by 30% at 12 weeks, but they remained lower than those of the sham control rats (P < 0.05). At this time, epididymal weights of all SCI rats remained lower than those of sham control rats (P < 0.05).


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  		Table 1. Testis and epididymis weights of SCI rats receiving hormone replacement

 
Spermatogenesis
In sham-operated control rats, the presence of qualitatively complete spermatogenesis is demonstrated by the presence of mature spermatids at the luminal edge of stage VII-VIII epithelium (Fig. 1AGo). Four weeks after SCI, abnormalities in spermatogenesis, including delay or failure in spermiation [as indicated by the presence of mature spermatids in the luminal edge of stages IX-XI epithelium, pyknosis, and/or vacuolization of spermatid nuclei, or incomplete spermatogenesis (Fig. 1BGo)] were observed in most of the SCI animals. Implantation of TC maintained qualitatively complete spermatogenesis in all SCI rats (n = 9) and facilitated normal spermiation, as indicated by a decrease in the occurrence of mature spermatids in stages X and XI epithelium (Fig. 1CGo). Daily injection of FSH for 14 days after SCI resulted in a more extensive degeneration of spermatogenic cells in SCI rats (Fig. 1DGo). The effects of FSH were further enhanced by TC implants, because these treatments resulted in regression of the seminiferous epithelium in most of the tubules in SCI rats (Fig. 2AGo).



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  		Figure 1. Photomicrographs of testicular histology. A, Control animal, showing the presence of well-organized seminiferous epithelium. The presence of mature spermatids in the luminal edge of stage VIII epithelium (VIII) demonstrates the completion of spermatogenesis. XII, A stage XII tubule showing mature pachytene spermatocytes (arrowheads) and elongated spermatids (x80). B, An untreated SCI rat, 4 weeks after SCI. Note the presence of mature spermatids in the luminal edge of stage IX epithelium (arrowheads) and presence of pyknotic nuclei (arrowheads) in the adjacent tubules (x80). C, An SCI rat, given 10 cm TC implants for 4 weeks, showing the absence of mature spermatids in a stage IX epithelium (x100). D, An SCI rat, given a daily injection of FSH for 2 weeks and hemicastrated 4 weeks after SCI. Note the presence of cell clumps in the lumen of the tubules, pyknosis of spermatogenic cell nuclei (arrowheads), and regression of the seminiferous epithelium (x80).

 


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  		Figure 2. A, An SCI rat, given a daily injection of FSH for 2 weeks and TC implants for 4 weeks, showing regression of the seminiferous epithelium in most tubules (x80). B, The second testis of the same rat shown in A, obtained 3 months after SCI. In this testis, active spermatogenesis was observed in over 80% of the tubules. Note the presence of mature spermatids at the luminal edge of stages VII-VIII epithelium (arrowheads) (x80). C, An SCI rat received TC implants and was killed 3 months after SCI. The presence of mature spermatids at the luminal edge of stages VII-VIII epithelium (arrowheads) demonstrates the persistence of qualitatively complete spermatogenesis. Note that mature spermatids were retained in an adjacent stage X tubule (x60). D, An untreated SCI rat, killed 3 months after SCI, showing total regression of the seminiferous epithelium (x40).

 
Unexpectedly, hemicastration of SCI rats 4 weeks post SCI resulted in a heavy loss of the animals. Of the 29 hemicastrated SCI rats, only 9 survived to the end of the experiment. The major cause of death was rupture of the bladder, because these animals lost the reflex voiding capability that occurs after recovery from spinal shock in SCI rats. The others died of weight loss after they stopped eating. Of the 2 SCI rats given FSH alone, 1 had active spermatogenesis in over 20% of the tubules. The seminiferous epithelium in the other FSH-treated SCI rat remained totally regressed. Of the 2 SCI rats that received both TC and FSH, active spermatogenesis was observed in 20% and 100% of the tubules (Fig. 2BGo). Active spermatogenesis was observed in 80 and 100% of tubules in the second testis of the 2 SCI rats bearing TC implanted for 12 weeks (Fig. 2CGo). However, abnormal spermatogenesis, as indicated by the failure in normal spermiation, persisted. The seminiferous epithelium of untreated SCI rats was either regressing or had regressed (Fig. 2DGo).

Spermatogonial proliferation
Four weeks after SCI, there was a 25 and 30% decrease in the number of Aal and A1 spermatogonia, respectively (P < 0.05, Fig. 3AGo). The decrease in spermatogonial number was not affected by TC implantation but was attenuated by FSH. In contrast, a combination of FSH and TC further decreased the number of Aal spermatogonia in SCI rats (P < 0.05). The numbers of type B spermatogonia and preleptotene spermatocytes also decreased after SCI (P < 0.05, Fig. 3BGo). This effect was not altered by TC implants or FSH when administered alone but was enhanced by the combination of T and FSH (P < 0.05).



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  		Figure 3. Effects of SCI and hormone replacement on the numbers of Aal and A1 spermatogonia (A) and type B spermatogonia and preleptotene spermatocytes (B), 4 weeks after SCI. Results are expressed as mean ± SEM cells per 100 Sertoli cell nucleoli of 4–5 rats. a, Different from sham control, P < 0.05; b, different from SCI, P < 0.05. The number in parentheses is the number of animals examined.

 
ITT
Four weeks after SCI, ITT concentrations in untreated SCI rats were not different from those of sham-operated controls (Fig. 4Go) and were not affected by daily injection of FSH during the first 2 weeks after SCI (P > 0.1). On the other hand, implantation of 10 cm TC suppressed ITT to a level that was below 5% of that in sham control rats (P < 0.001). ITT concentration in the FSH/TC-treated SCI rats was not measured, because of insufficient materials.



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  		Figure 4. Testicular T concentrations in SCI rats with or without hormone replacement. Results are expressed as mean ± SEM ng/g tissue (n = number of animals measured). a and b, Different from sham control, and SCI rats, respectively, P < 0.001.

 
Sertoli cell proteins mRNA
Four weeks after SCI, there was a 30–40% increase in AR mRNA (P < 0.05) in the testes of SCI rats; this increase was prevented by TC implants (Fig. 5Go). Though FSH alone did not affect the level of AR mRNA, it prevented the suppressive effect of TC on AR mRNA. FSH-R mRNA in the testes of untreated SCI rats was not different from that of sham-operated controls (Fig. 5Go). FSH treatment produced more than 40% higher FSH-R mRNA in the testes of SCI rats (P < 0.05), and this effect was further enhanced by TC implantation (P < 0.05).



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  		Figure 5. Northern blot analysis of mRNA transcripts for AR and FSH-R. A, Representative radiographs for 2 sham controls and 2 experimental samples from each treatment group. Each lane contained 15 µg poly (A)+ RNA, and the radiographs were developed after 6 days of exposure; B, quantitative analysis of AR and FSH-R mRNA levels after they were normalized against the amount of 18s ribosomal RNA in each sample. Results are expressed as mean ± SEM percent of sham controls in each blot. a, Different from sham control, P < 0.05; b, different from SCI, P < 0.05 (n = number of animals examined).

 
The levels of both ABP and Trf mRNA in the testes of SCI rats were within the range of sham-operated controls 4 weeks after SCI (Fig. 6Go). TC implantation alone did not affect ABP mRNA, but it resulted in a more than 50% decrease in Trf mRNA (P < 0.05). On the other hand, the levels of both ABP and Trf mRNA were significantly higher in the testes of SCI rats given FSH injections for 14 days (P < 0.05), and this increase was enhanced by TC implantation (P < 0.05). The level of the 0.9-kb hemiferrin mRNA in the testes of SCI rats was not statistically different from that of the sham-operated controls and was not affected by hormone treatments.



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  		Figure 6. Northern blot analysis of the effects of SCI and hormone replacement on mRNA transcripts for transferrin (Trf), hemiferrin (Hemif), and ABP. A, Representative radiographs of 2 sham controls and 2 experimental samples from each treatment group. Each lane contained 15 µg poly (A)+ RNA, and the radiographs were developed after 1 or 2 days of exposure. B, Quantitative analysis of the levels of Trf and ABP mRNA after they were normalized against 18s ribosomal RNA in each sample. Results are expressed as mean ± SEM percent of sham controls in each blot. a, Different from sham control, P < 0.05; b, different from SCI, P < 0.05 (n = number of animals examined).

 

   Discussion
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
In the rat, undifferentiated paired type A spermatogonia divide to form Aal spermatogonia, which become mitotically active A1 spermatogonia. These A1 spermatogonia undergo a series of mitotic divisions resulting in the formation of preleptotene spermatocytes that enter meiosis (20). A decrease in the number of Aal and A1 spermatogonia after hypophysectomy (10) suggests that proliferation of undifferentiated spermatogonia might be androgen and/or FSH dependent. A decrease in serum FSH and ITT levels shortly after SCI (5), and the number of Aal and A1 spermatogonia at later times (8, 9), suggest a possible cause-effect relationship between these phenomena. Current results of a comparable 25–30% decrease in Aal and A1 spermatogonia in untreated SCI rats (which had normal ITT concentrations) and in those TC implanted SCI rats (which had <5% normal ITT) suggest that such decrease is not caused by a decrease in ITT concentrations. Although FSH alone lessened the decrease in Aal and A1 spermatogonia in SCI rats, a combination of FSH and TC implants resulted in a greater decrease in these spermatogonia than did TC alone. This effect is different from that in hypophysectomized rats (21, 22) and monkeys (23, 24), in which FSH and T act synergistically to restore spermatogonial populations. Taken together, these results suggest that the mechanisms leading to the decrease in undifferentiated spermatogonia after SCI probably are not related directly to the availability of FSH or T.

Presence of spermatogenic abnormalities in SCI rats while ITT concentrations were normal is consistent with nonendocrine mechanisms mediating the effects of SCI on spermatogenesis (8). However, prevention of some of these abnormalities during the early phase of SCI and maintenance of qualitatively complete spermatogenesis during the chronic phase of SCI by exogenous T suggests that androgen-dependent cellular events might be involved in the spermatogenic effects of SCI. The beneficial effects of exogenous T were best demonstrated in FSH/TC-treated SCI rats in which one testis was severely regressed at the end of the 4th week, whereas active spermatogenesis was present in the other testis 3 months after SCI. Previously, Meistrich et al. (25) postulated that suppression of ITT of the rat by exogenous T or GnRH-antagonist might alter local paracrine mechanisms that, in turn, may modulate microenvironment of the seminiferous epithelium and facilitate spermatogenic recovery after irradiation or chemotherapy. Whether similar mechanisms are responsible for the beneficial effects of exogenous T on spermatogenesis of SCI rats remained to be tested.

On the other hand, enhancement of seminiferous epithelial regression during the acute phase of SCI by FSH alone or in combination with TC implants was paradoxical and unexpected. This is different from the beneficial effects of the identical FSH and TC regimens on spermatogenesis in hypophysectomized rats, in which FSH facilitates the effects of T on spermiogenesis (11). Because spermatogonial proliferation was persisting and preleptotene spermatocytes were present in FSH and TC/FSH-treated SCI rats 4 weeks after surgery, degeneration of meiotic and postmeiotic cells at this time most likely results from impairment of Sertoli cell functions essential for the differentiation of these cells.

Both FSH and T are essential for Sertoli cell functions and exert their effects on spermatogenesis through respective receptors in Sertoli cells (26, 27). Maintenance of normal levels of testicular FSH-R mRNA 4 weeks after SCI is consistent with the presence of normal serum FSH level at this time (5). However, an increase in FSH-R mRNA level in those rats given FSH injections and the fact that this effect was exaggerated by TC implants suggest a stimulation of the FSH-R gene. This is different from the negative effect of FSH and negative (or lack of) effects of T on FSH-R mRNA in cultured Sertoli cells and in the testes of hypophysectomized prepubertal or nonSCI adult rats (16, 28). Furthermore, an increase in testicular AR mRNA levels in SCI rats whereas ITT concentrations were normal, and normal AR mRNA levels in TC-treated SCI rats that had reduced ITT concentrations, suggest that autoregulation of AR gene by its own ligand may have been compromised. Although stimulation of AR mRNA by FSH in cultured Sertoli cells has been reported (29, 30), the higher AR mRNA level in TC/FSH-treated SCI rats is unlikely a direct result of FSH stimulation because: 1) AR mRNA level was not significantly increased in those SCI rats that received FSH alone; and 2) FSH injection had stopped 2 weeks before hemicastration. The increase in AR mRNA may result from an increase in the sensitivity of AR gene to androgen, because expression of AR in Sertoli cells has been reported to be stimulated by androgen and was greatly reduced after GnRH-antagonist treatment (31, 32). Thus, increased expression of AR and FSH-R mRNA in FSH- and/or T-replaced SCI rats may reflect a change in the regulation of these genes, perhaps attributable to the disruption of normal neural input to the testes as the result of SCI and/or FSH pretreatment.

The presence of normal levels of ABP and Trf mRNA in the testes of SCI rats is consistent with our previous observation (5). The lowered Trf mRNA in TC-implanted SCI rats is likely caused by the decrease in ITT and is consistent with the androgen-dependent expression of this protein (28, 33). In contrast, both ABP and Trf mRNA levels were significantly higher in SCI rats that received FSH treatment, and this effect was augmented by TC implantation. These results are different from that in nonSCI adult rats, in which ABP and Trf mRNA levels were decreased after FSH and/or T treatment (28). Although a greater loss of spermatogenic cells in the FSH-treated SCI rats may increase Sertoli cell density and contribute to higher levels of ABP and Trf mRNAs, this possibility is discounted by unequal increases in these mRNA transcripts within each treatment group. Because the level of FSH-R mRNA was also higher in FSH-treated SCI rats, the increase in ABP and Trf mRNA levels in these SCI rats may reflect a stimulation of respective genes by FSH caused by the presence of a higher abundance of FSH-R. In Sertoli cells isolated from immature rats, cAMP and protein kinase activities can be modulated by adrenergic agonist, isoproterenol (34, 35). In addition, FSH regulation of Sertoli cell proliferation (36) and production of ABP and inhibin have been reported to be modulated by neural peptide, endorphin (37, 38). These results suggest possible neural-FSH interactions in the control of Sertoli cell function. Thus, alteration of Sertoli cell functions, as suggested by an increase in ABP and Trf mRNA in FSH-treated SCI rats, might reflect perturbation of such interaction. These changes may impair the Sertoli cell functions essential for the differentiation of spermatogenic cells, thus contributing to the enhanced regression of spermatogenesis in the FSH-treated SCI rats.

In summary, current results demonstrate that regression of spermatogenesis in SCI rats can be partially prevented by exogenous T but is paradoxically enhanced by FSH. These effects are associated with altered responses of the mRNA transcript for Sertoli cell proteins to exogenous T and FSH, thus suggesting perturbation of Sertoli cell function and its regulation. Such changes may alter the endocrine and/or paracrine microenvironment within the seminiferous epithelium and tamper with the proliferation and/or differentiation of spermatogenic cells. The latter may thus result in abnormalities in spermatogenesis seen during different stages of SCI. Maintenance of qualitatively complete spermatogenesis in chronic SCI rats by exogenous T suggests the feasibility of using endocrine regimens to impede the deleterious effects of SCI on spermatogenesis. Further understanding of signal events mediating the beneficial effects of T on spermatogenesis, and the changes in the responses of Sertoli cells to FSH in SCI rats, may unravel the mechanisms responsible for the deleterious effects of SCI on spermatogenesis. Such studies will provide mechanistic rationale for the development of endocrine regimens in the prevention and treatment of SCI-related male infertility and therefore are warranted.


   Acknowledgments
 
We would like to thank the following investigators for their generous gift of cDNA used in the current experiment: Drs. M. Griswold (transferrin and FSH-R), D. Joseph (ABP), and SC Liao (androgen receptor). The editorial comments of Randi Rutan are greatly appreciated.


   Footnotes
 
Address all correspondences and requests for reprints to: Dr. H. F. S. Huang, Department of Surgery Section of Urology, UMD-New Jersey Medical School, 185 South Orange Avenue, Newark, New Jersey 07103.

1 This work was supported by Veterans Affairs Rehabilitation Research and Development Services (B885-RA). Back

Received June 8, 1998.


   References
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

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