Journal of Andrology Track the topics, authors and articles important to you
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kamiya, H.
Right arrow Articles by Kohri, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kamiya, H.
Right arrow Articles by Kohri, K.
Journal of Andrology, Vol. 24, No. 6, November/December 2003
Copyright © American Society of Andrology

Effect of Simulated Microgravity on Testosterone and Sperm Motility in Mice

HIROYUKI KAMIYA*, SHOICHI SASAKI*, TAKAHITO IKEUCHI*, YUKIHIRO UMEMOTO*, HIROYUKI TATSURA*, YUTARO HAYASHI*, SHIGEO KANEKO{dagger} AND KENJIRO KOHRI*

From the * Department of Nephro-urology, Nagoya City University Graduate School of Medical Science, Nagoya, Japan; and the {dagger} Department of Urology, Asahikawa Medical College, Asahikawa, Japan.

Correspondence to: Dr Hiroyuki Kamiya, Department of Nephro-urology, Nagoya City University Graduate School of Medical Science, 1, Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan (e-mail: kamihiro{at}med.nagoya-cu.ac.jp).
Received for publication September 17, 2002; accepted for publication May 27, 2003.

   Abstract
Top
 Abstract
Materials and Methods
 Results
 Discussion
 References
 
We examined changes in the serum testosterone level and in sperm in the testis and epididymis by using tail-suspended mice, which are a simulation model of the body fluid shift in space, to evaluate the possibility of spermatogenesis failure in space environment. We also studied pathological disorders of the testis in the tail-suspended mice. Tail suspension was imposed with a tail harness to a degree at which the hindlegs of mice did not touch the floor of the housing unit. In control mice, the tail was similarly fixed with a tail harness to impose the same stress, except that a hindleg remained on the floor. Body weight was not significantly different between the 2 groups during 7 days, and testicular weight was significantly different. The testosterone level was significantly lower in the tail-suspended group (0.71 ± 1.24 ng/mL) than in the control group (2.38 ± 3.50 ng/mL; P < .05). Microscopy with hematoxylin and eosin (HE) and periodic acid-Schiff (PAS) staining showed a small proportion of seminiferous tubules with impairment of spermatogenic function in the tail-suspended group, and multinucleated giant cells were occasionally noted. Terminal deoxynucleotidyl tranferase-mediated nick end-labeling staining revealed positive cells even in animals in which impairment was considered to be mild based on HE and PAS staining. Many cells showed intense p53 immunostaining compared to the control group, with more intense staining of the nucleus in the tail-suspended group. The proportion of motile sperm was slightly but not significantly reduced in the tail-suspended group. However, the mean movement velocity of the motile spermatozoa was significantly decreased.

     Key words: Tail suspension, space, simulated weightlessness, testicular function, spermatogenesis, mouse


The effects of space environment on reproduction should be evaluated from diverse points of view. Subjects of interest include the effects of a vacuum on embryogenesis, the effects of temperature and humidity on embryonic development and spermatogenesis, the possibility that space radiation or magnetic fields may cause embryonic or genetic disorders, and the effects of stress on embryonic development and hormone balance. As potentially even more serious problems, we must consider spermatogenesis failure in males because of a reduction in the testicular blood flow caused by the shift of body fluids in the cranial direction in a microgravity state and the effects of this state on fertilization and development. The effects of a microgravity environment on reproduction are thus expected to be one of the major themes in the coming space age.

A stay in space for 6 months is planned for 2006, and stays in space for even longer periods are anticipated in the near future. We examined changes in the sperm in the testis and epididymis by using tail-suspended mice, which are a simulation model of the body fluid shift in space, to evaluate the possibility of spermatogenesis failure in space.

The tail-suspension model has been used in studies of muscle atrophy and osteoporosis observed in microgravity states (Globus et al, 1986; Morel et al, 1997; Halet et al, 1999; Wimalawansa et al, 1999). However, the tail-suspension model also is considered to be a model of body fluid shift (Royland et al, 1994), and a few studies have used tail-suspended rats as a spermatogenesis failure model. Those studies to date have demonstrated decreases in the serum testosterone level, that is, disorders of Leydig cells, but failed to demonstrate clear disorders of Sertoli cells or no effect on germ cells (Hargens et al, 1984; Deaver et al, 1992; Hadley et al, 1992). In this study, we examined changes in the serum testosterone level and in sperm in the testis and epididymis by using tail-suspended mice, to evaluate the possibility of spermatogenesis failure in a microgravity environment. We also studied pathological disorders of the testis in the tail-suspended mice.


   Materials and Methods
Top
 Abstract
 Materials and Methods
Results
 Discussion
 References
 
Animals

B6D2F1 male mice at starting age 10 weeks (average weight 25.6 g, Japan SLC, Shizuoka, Japan) were used. Animals were randomized according to weight, and for each experiment the mice were divided into 2 groups (17 mice/group): tail-suspended mice and control mice. After the mice were put in a metabolism cage and kept there for 7 days, tail suspension was performed by following the design described by Wronski and Morey-Holton (1987). The mice were anesthetized by means of an intramuscular injection of pentobarbital (50 mg/kg body weight). Conscious mice were loosely restrained in a towel while their tails were mildly abraded with gauze soaked in 70% ethanol. Tincture of benzoin was sprayed on the skin for protection against adhesive tape irritation and allowed to dry. A strip of orthopedic tape attached to a plastic suspension bar was applied to the lateral sides of the tail. The tape was then secured by wrapping a strip of stockette around the tail. Each mouse was then attached via the plastic suspension bar to a pulley system mounted on the top of an acrylic housing unit. The 17 mice suspended in this manner were allowed freedom of movement and access to food and water. The torso was inclined at a degree at which the hind legs of the mice did not touch the floor of the housing unit. For control mice, the tail was fixed with a tail harness to impose stress by the equivalent body motion fixation, but they had a hind leg on the floor. Drinking water and solid feed appropriate for reproduction (Oriental Yeast, Tokyo, Japan) were provided ad libitum. The room in which the animals were housed was maintained at 24°C with a 12-hour light : dark cycle. After 7 days, the testes and epididymides in each group were exposed after blood collection from the inferior vena cava under pentobarbital anesthesia. Each testis was inspected, separated from the spermatic cord and epididymis, and weighed.

Structural Organization and Apoptosis of the Testis

Testicular tissues were fixed in 4% paraformaldehyde solution, embedded in paraffin, and cut in thin (5-µm) sections, which were then stained with hematoxylin and eosin (HE), periodic acid-Schiff (PAS) (Takahashi et al, 1994), or anti-p53 polyclonal antibody (Santa Cruz Bio., Santa Cruz, California). Apoptotic cells in the testicular tissues were identified by the terminal deoxynucleotidyl tranferase-mediated nick end-labeling (TUNEL) assay by using the commercial TdT-FragEL DNA Fragmentation Detection Kit (Wakojunyaku, Osaka, Japan) according to the manufacturer's instructions with some modifications (Wang et al, 1998). Endogenous peroxidase was inactivated in the slices with H2O2/methanol after deparaffinization and proteolysis was performed by using proteinase K. Incubation with terminal deoxynucleotidal transferase was carried out at 37°C for 1 hour. The sections were incubated with antidigoxigenin antibody at room temperature for 30 minutes. The coloring was done with 3,3'-diaminobenzidine tetrahydrochloride. The apoptotic index was determined by counting the number of apoptotic cells in randomly picked microscopic fields (precisely 2.25 mm2, with a minimum of 25 seminiferous tubules) of a tissue section by following the method of Zini et al (1998).

Radioimmunoassays for Serum Testosterones

Blood taken from each mouse was allowed to clot and was then centrifuged, and serum was collected. Testosterone levels were determined in duplicate by radioimmunoassay, based on testosterone-specific antibody immobilized to the wall of a polypropylene tube. Commercially available assay kits (Diagnostic Products Corporation, Los Angeles, Calif), which included 125iodine-labeled testosterone, rabbit antiserum, and goat anti-rabbit gamma globulin, were used (Sayegh et al, 1990; Houle and Taketo, 1992). The sensitivity of the assay ranged from 0.4 to 160 ng/mL. The antiserum is highly specific for testosterone, with very little cross-reactivity with other compounds that might be present in samples. The cross-reactivity with 5-alpha-dihydotestosterone is less than 5%. Lipemia, bilirubin, and hemolysis do not interfere with the assay.

Analysis of Spermatozoan Motility

The presence of spermatozoa was confirmed by cutting the head of the epididymis and squeezing it into human tubular fluid (Irvine Scientific, Santa Ana, Calif) immediately after exposure of the epididymis. The spermatozoa were allowed to swim up and were incubated for 1 hour in a 5% CO2/95% air incubator at 37°C. The spermatozoan motility was analyzed by using a spermatozoan motion automatic analyzer HTM 2030 (Hamilton-Thorn Research Co, Boston, Mass) to measure motility (%), path velocity (µm/s), mean track speed (µm/s), mean progressive velocity (µm/s), mean linearity (%), mean amplitude of lateral head displacement (µm), and mean beat frequency (Hz).

Statistical Analysis

The results are presented as means ± standard deviations (SD). Statistical analysis was performed by Student's t test, and differences were considered significant when P was <.05.


   Results
Top
 Abstract
 Materials and Methods
 Results
Discussion
 References
 
The testicular weight was significantly different between the tail-suspended and control mice. The body weight change (weight after as compared to before the experimental treatment) was -1.14 g in the tail-suspended group and -0.80 g in the control group (not significantly different; Table 1).


View this table:
[in this window]
[in a new window]
  		Table 1. Characteristics of tail-suspended mice and control mice*
 

Microscopy with HE and PAS staining showed that in a small fraction of seminiferous tubules, impairment of approximately 5% of spermatogenic function occurred in the tail-suspended group. Impairment of spermatocytes beyond the pachytene stage was observed. Almost no spermatozoa were found. Little disturbance of the arrangement of cells was found in the organ (Figure 1A). Marked failure of spermatogenesis was observed by stage VII. Multinucleated giant cells were occasionally noted (Figure 1C).



View larger version (153K):
[in this window]
[in a new window]
  		Figure 1. Seminiferous tubule morphology analyzed with periodic acid-Schiff staining by light microscopy of tail-suspended mice (A, B and C) and of control mice (D, E). The arrangement of the cells was disturbed in the seminiferous tubules of tail-suspended mice, and spermatogenic cells were decreased (B). The disturbance of the arrangement was slight in (A). The impairment of spermatogenesis was strong by stage VII (B). The impairment seemed to be marked for spermatocytes after pachytene. The interstitial tissue was maintained (A, B). Multinucleated giant cells (arrow), which indicate the failure of the spermatid, were observed sporadically (C). In controls, the structure was normal and the cells were not damaged (D, E). A, D: magnification 100x. Bar = 100 µm. B, C, and E: magnification 400x. Bar = 10 µm.

 

The TUNEL staining revealed that the apoptotic index (Zini et al, 1998) was significantly increased in the tail-suspended group (11.13 ± 5.35) compared with that in the control group (5.25 ± 2.73; P < .05). TUNEL-positive cells were observed even in the animals in which the impairment of spermatogenesis was considered to be mild based on HE and PAS staining. The apoptotic index was shown to be greater in the tail-suspended group (4.25 ± 1.92) than in the control group (2.88 ± 1.27) by p53 immunostaining, with more intense staining of the nucleus in the tail-suspended group (Figure 2).



View larger version (121K):
[in this window]
[in a new window]
  		Figure 2. Detection of apoptosis by terminal deoxynucleotidyl tranferase-mediated nick end-labeling (TUNEL) staining (A, B, C and D). TUNEL-positive cells were increased in the tail-suspended mice, and the level of apoptosis seemed to increase. Simultaneously, the cytoplasm was observed to be diminished in the same seminiferous tubules. TUNEL-positive cells were observed (arrow) in (B). Few positive cells occurred in control mice (C, D). After tail suspension, an increase of apoptosis-positive cells occurred, as shown by anti-p53 immunostaining (E, F), and strong staining of the nucleus was observed (arrow) (F). Few positive cells were found in control mice (G, H). A, C, E, and G: magnification 100x. Bar = 100 µm. B, D, F, and H: magnification 400x. Bar = 10 µm.

 

The testosterone concentration was significantly lower in the tail-suspended group (0.74 ± 1.28 ng/mL) than in the control group (2.38 ± 3.50 ng/mL; Table 1).

Although no significant decrease occurred in the proportion of motile sperm, significant decreases in the path velocity, mean track speed, and mean progressive velocity, which are parameters of sperm motility, indicated impairment of the motor capacity of individual sperm despite the lack of a marked decrease in the proportion of motile sperm (Table 2).


View this table:
[in this window]
[in a new window]
  		Table 2. Analysis of spermatozoan motility*
 


   Discussion
Top
 Abstract
 Materials and Methods
 Results
 Discussion
References
 
As mankind enters the space age, whether humans can maintain a normal life cycle, including reproduction, in space becomes a critical problem. Reproduction experiments in microgravity environments have been carried out with insects, fish, amphibians, and birds. The complete life cycle of the vinegar fly was shown to occur (Miquel and Philpott, 1978) during a space trip, and normal pregnancy and normal early embryogenesis have been confirmed in the killifish in space (Serova et al, 1993). In amphibians, different results were obtained in experiments in a clinostat, which is a device that simulates a microgravity environment, compared to those during a space trip. Xenopus laevis was reported to develop normally in the clinostat (Smith and Neff, 1986), whereas in space, its eggs could be fertilized in vitro to produce offspring that showed slight, reversible abnormalities during an early phase after hatching, and grew into nearly normal tadpoles (Souza et al, 1995). In birds (quail), hatching and early development were reported to occur during a space trip (Boda et al, 1991). In mammals, the development of pups obtained by allowing male rats to mate after a space flight of 2.5-3 months on Biosatellite Cosmos 1129 in 1982 was delayed, and pups obtained from female rats that had a flight on a Space Shuttle at days 9-20 of pregnancy in 1996 grew normally, but reports concerning the effect of space flight on spermatogenic ability or sperm motility are still scarce and insufficient (Amann et al, 1992). In a microgravity environment, body fluids are thought to be distributed evenly in the body, so that blood distributed in the upper one half of the human body is considered to increase by about 2 L compared with the volume in a normal gravity state, causing facial edema and cardiovascular responses. These changes in the body fluid balance may affect hormones and reproductive organs (Merrill et al, 1992; Maillet et al, 1998; Strollo et al, 1998).

After 7 days of tail suspension, testicular weight was significantly different between the tail-suspended mice and control mice. The body weight change (weight after compared with before the experimental treatment) was not significantly different between the tail-suspended group and controls. The testosterone level was significantly lower in the tail-suspended group compared with controls. The decrease in testosterone was in agreement with the finding of Merrill et al (1992), who examined changes in the serum electrolyte and hormone levels in space-flight and tail-suspended rats, and the decrease in testosterone suggests that testosterone secretion is reduced because of a reduction in the testicular blood flow associated with the cranial shift of body fluids. On the other hand, Tash et al (2002) reported that testosterone decreased early in their experiment but recovered by the end of the 6-week experiment. A compensatory mechanism to regulate the testosterone level may function in long-term tail suspension. Stress caused by tail suspension was not considered to affect the results, because no difference was found in body weight loss between the 2 groups of mice in our study.

Microscopy with HE and PAS staining showed a small proportion of seminiferous tubules with impairment of spermatogenic function in the tail-suspended group. Impairment was observed in spermatocytes after pachytene, and no spermatozoa were present. Multinucleated giant cells were occasionally noted. Multinucleated giant cells often are observed after exposure to drugs that cause testicular disorders (Rotter et al, 1993; Singh et al, 1995; Huyun et al, 2000; Li et al, 2001) and also have been reported to appear after a weight-reducing diet (Umapathy, 1992) and trauma (Del Conte, 1975). Therefore, their appearance is considered to suggest possible rapid changes in hormone levels, a decrease in the body fluid volume, or both.

The results of TUNEL staining indicated that apoptotic cells were significantly increased. Therefore, apoptosis is considered to be involved in the impairment of the seminiferous tubules. Apoptosis is important for the elimination of abnormal embryonic cells and the maintenance of homeostasis of normal cells. Various hormonal regulatory mechanisms in the process of spermatogenesis have been reported to involve apoptosis (Tapanainen et al, 1993; Sinha Hikim and Swerdloff, 1999).

Many cells also were intensely stained by p53 immunostaining, and staining of the nucleus was particularly intense. This suggests an involvement of p53 in the process of apoptosis in these cells (Amundson et al, 1998).

The proportion of motile sperm was slightly but not significantly reduced in the tail-suspended group. However, path velocity and mean track speed, which are parameters of sperm motility, were significantly decreased, indicating impairment of the motor capacity of individual sperm despite the lack of a marked decrease in the proportion of motile sperm. Tash et al (2002) found that 6 weeks of tail suspension inhibited spermatogenesis in rats. The experiments described here indicate that testicular atrophy starts and apoptosis of germ cells increases within 7 days of tail suspension. In conclusion, a microgravity state of short duration appears to have slight effects on sperm functions and may induce irreversible testicular atrophy if prolonged.


   Footnotes
 
Supported in part by a Grant-in-Aid for Scientific Research (09470350) from the Ministry of Education, Science and Culture, Japan, to Dr Shoichi Sasaki; a Grant-in-Aid for Research from Nagoya City University to Dr Shoichi Sasaki; and a Grant for Ground Research for Space Utilization promoted by National Space Development Agency of Japan (NASDA) and Japan Space Forum to Dr Shoichi Sasaki.


   References
Top
 Abstract
 Materials and Methods
 Results
 Discussion
 References
 
Amann RP, Deaver DR, Zirkin BR, et al. Effect of microgravity or simulated launch on testicular function in rats. J Appl Physiol. 1992; 73:174S-185S.

Amundson SA, Myers TG, Fornace AJ Jr. Roles for p53 in growth arrest and apoptosis: putting on the brakes after genotoxic stress. Oncogene. 1998; 17:3261-3270.[Medline]

Boda K, Mereskok GI, Sabo V, Seperev EJ, Gurjeva TS, Jurani M, Kostal L. Embryonic development of Japanese quail under microgravity conditions. Physiologist. 1991; 34:59-61.

Deaver DR, Amann RP, Hammerstedt RH, Ball R, Veeramachaneni DNR, Musacchia XJ. Effect of caudal elevation on testicular function in rats separation of effects on spermatogenesis and steroid genesis. J Androl. 1992; 13:224-231.[Abstract/Free Full Text]

Del Conte E. Multinucleate spermatogenic cells by traumatic hemorrhagic suffusion in lizard testis. Cell Pathol. 1975; 18:297-305.

Globus RK, Bikle DD, Halloran B, Morey-Holton E. Skeletal response to dietary calcium in a rat model simulating weightlessness. J Bone Miner Res. 1986; 1:191-197.[Medline]

Hadley JA, Hall JC, Obrien A, Ball R. Effects of a simulated microgravity model on cell structure and function in rat testis and epididymis. J Appl Physiol. 1992; 72:748-759.[Abstract/Free Full Text]

Halet G, Viard P, Morel JL, Mironneau J, Mironneau C. Effects of hindlimb suspension on cytosolic Ca2+ and [3H] ryanodine binding in cardiac myocytes. Am J Physiol. 1999; 276:H1131-1136.

Hargens AR, Steskal J, Johansson C, Tipton CM. Tissue fluid shift, forelimb loading and tail tension in tail-suspended rats. Physiologist. 1984; 27:S37-S38.

Houle A-M, Taketo T. True hermaphrodites: an experimental model in the mouse. J Urol. 1992; 148:672-676.[Medline]

Huyun PN, Hikin AP, Wang C, et al. Long-term effect of triptolido on spermatogenesis, epididymal sperm function, and fertility in male rats. J Androl. 2000; 21:p689-699.

Li GX, Kang KS, Lee YS. 2-Bromopropan induced germ cell apoptosis during spermatogenesis in male rat. J Vet Med Sci. 2001; 63:373-382.[Medline]

Maillet A, Titze J, Gushin V, Nichiporuk I, Kirsch KA, Gharib C, Gauquelin-Koch G. Hormonal changes during a 20-week confinement. Aviat Space Environ Med. 1998; 69:1045-1051.[Medline]

Merrill AH Jr, Wang E, Mullins RE, Grindeland RE, Popova IA. Analyses of plasma for metabolic and hormonal changes in rats flown aboard COSMOS 2044. Physiology. 1992; 73:132S-135S.

Miquel J, Philpott DE. Effect of weightlessness on the genetics and aging process of Drosophila melanogaster. In: Rosenzweig N, Souza KA eds. Final Report: U.S. Experiments Flown on the Soviet Satellite Cosmos 936 (NASA Technical Memorandum 78525). 1978 :32-59.

Morel JL, Boittin FX, Halet G, Arnaudeau S, Mironneau C, Mironneau J. Effect of a 14-day hindlimb suspension on cytosolic Ca2+ concentration in rat portal vein myocytes. Am J Physiol. 1997; 273:H2867-2875.

Rotter V, Schwartz D, Almon E, Goldfinger N, Kapon A, Meshorner A, Doneower LA, Levine AJ. Mice with reduced levels of p53 protein exhibit the testicular giant-cell degenerative syndrome. Proc Natl Acad Sci USA. 1993; 90:9075-9079.[Abstract/Free Full Text]

Royland JE, Weber LJ, Fitzpatrick M. Testis size and testosteron levels in a model for weightlessness. Life Sci. 1994; 54:545-554.[Medline]

Sayegh JF, Kobor G, Lajtha A, Vadasz C. Effects of social isolation and the time of day on testosterone levels in plasma of C57BL/6By and BALB/cBy mice. Steroids. 1990; 55:79-82.[Medline]

Serova LV. Changing gravity level and the development of animals. Physiologist. 1993; 36:31-33.

Singh AK, Dominic CJ. Testicular toxicity of win18446 in the laboratory mouse. Reprod Toxicol. 1995; 9:475-481.[Medline]

Sinha Hikim AP, Swerdloff RS. Hormonal and genetic control of germ cell apoptosis in the testis. Rev Reprod. 1999; 4:38-47.[Abstract]

Smith RC, Neff AW. Organization of Xenopus egg cytoplasm: response to stimulated microgravity. J Exp Zool. 1986; 239:365-378.[Medline]

Souza KA, Black SD, Wassersug RJ. Amphibian development in the virtual absence of gravity. Proc Natl Acad Sci USA. 1995; 92:1975-1978.[Abstract/Free Full Text]

Strollo F, Riondino G, Harris B, Strollo G, Casarosa E, Mangrossa N, Ferretti C, Luisi M. The effect of microgravity on testicular androgen secretion. Aviat Space Environ Med. 1998; 69:113-136.

Takahashi M. The Spermatogenesis Cycle of the Rat. Seminiferous Tubule Atlas for Rat, Mouse, Dog. For the Testicular Toxicity Evaluation [in Japanese]. Tokyo, Japan: Soft Science Co; 1994 :1-38.

Tapanainen JS, Tilly JL, Vihko KK, Hsueh AJ. Hormonal control of apoptotic cell death in the testis: gonadotropins and androgens as testicular cell survival factors. Mol Endocrinol. 1993; 7:643-650.[Abstract]

Tash JS, Johnson DC, Enders GC. Long-term (6-wk) hindlimb suspension inhibits spermatogenesis in adult male rats. J Appl Physiol. 2002; 92:1191-1198.[Abstract/Free Full Text]

Umapathy E. Diet-induced changes in the male reproductive system of rat. Andrologia. 1992; 29:49-58.

Wang RA, Nakane PK, Koji T. Autonomous cell death of mouse male germ cells during fetal and postnatal period. Biol Reprod. 1998; 58:1250-1256.[Abstract/Free Full Text]

Wimalawansa SM, Wimalawansa SJ. Simulated weightlessness-induced attenuation of testosterone production may be responsible for bone loss. Endocrine. 1999; 10:253-260.[Medline]

Wronski TJ, Morey-Horton ER. Skeletal response to simulated weightlessness: a comparison of suspension techniques. Aviat Space Environ Med. 1987; 58:63-68.[Medline]

Zini A, Abitbol J, Girardi SK, Schulsinger D, Goldstein M, Schlegel PN. Germ cell apoptosis and endothelial nitric oxide synthase (eNOS) expression following ischemia-reperfusion injury to testis. Arch Androl. 1998; 41:57-65.[Medline]





This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kamiya, H.
Right arrow Articles by Kohri, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kamiya, H.
Right arrow Articles by Kohri, K.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS