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1.
The aim of this work was to study effects of ketotifen fumarate(KF)on prevention of tissue damage in testes of rats with experimental autoimmune orchitis(EAO)and on the contralateral testis in a model of prolonged testicular cord torsion(TCT).Rats with EAO or TCT were injected intraperitoneally once daily with KF or saline solution(vehicle group).Incidence and severity of testicular damage were evaluated by histopathology using an EAO score or a Johnsen score.Mast cells(MC)were identified by histochemistry and quantified.In EAO model,KF significantly reduced severity of histopathological testicular damage compared to rats in the vehicle group.KF also reduced the number of testicular MC compared to vehicle group.Similarly,in TCT model,multifocal damage of the contralateral testis was observed 30 days after testicular torsion characterized by sloughing of the germinal epithelium,seminiferous tubule atrophy,and interstitial edema.Focal signs of inflammation and fibrosis of seminiferous tubular walls were also observed.In contrast,sections of contralateral testis of rats injected with KF and killed 30 days after surgery showed normal histological features.A significant decrease in the number of MC was observed in rats treated with KF compared to untreated animals.In conclusion,we demonstrated that treatment with KF reduced testicular inflammatory process and MC infiltrates in both EAO and TCT models.The results suggest a promising treatment for infertile male patients with testicular pathologies associated with inflammation and germ cell loss.  相似文献   

2.
To investigate the relationship between germ cell apoptosis and expres-sion of iNOS in experimentally torsed testes in rats. Adult male rats weresubjected to unilateral testicular torsion of 720 g for two hours. Six days lat-er, testes were collected for the detection of iNOS expression with immuno-histochemical method and germ cell apoptosis with TdT-mediated dUTP-X  相似文献   

3.
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)  相似文献   

4.
Germ cell apoptosis induced by ureaplasma urealyticum infection   总被引:19,自引:2,他引:17  
Aim: To study the effect of Ureaplasma urealyticum (UU) infection on germ cell apoptosis of male rats. Methods: Male rats were infected artificially with UU serotype 8 (T960). Morphological changes of germ cells in the seminiferous tubules and the lumen of the epididymides were observed under the light microscope. Fluorescence-conjugated polyclonal antibodies to Fas and Fas ligand (FasL) were used to localize Fas and FasL. TUNEL staining of germ cells and Sertoli cells was performed by the AKPase method. TUNEL-positive rate ( % positive cells) and TUNEL-positive area (area occupied by stained cells) were analysed by KS400 Image Analysis System. The DNA laddering analysis was performed by agarose gels electrophoresis. Results: In those rats infected with UU: (1) Exfoliated germ cells were dramatically increased. Many multinucleated giant cells were found in the seminiferous tubules and the lumen of the epididymides. (2) The number of TUNEL-positive cells and the TUNEL-positive area were significantly increased. (3) The expression of Fas and FasL in germ cells and Sertoli cells was up-regulated. (4) Discrete bands of fragmented DNA were found in the testicular cells. Conclusion: In male rats, germ cell apoptosis was increased in UU infection.  相似文献   

5.
Aim: To evaluate the effects of 60 Hz extremely low frequency (ELF) elelctromagnetic field (EMF) exposure on germ cell apoptosis in the testis of mice. Methods: Adult male BALB/c mice (7 weeks of age) were exposed to a 60 Hz EMF of 0.1 mT or 0.5 mT for 24 h/day. A sham-exposed group served as the control. After 8 weeks of exposure, the mice were sacrificed. Germ cell apoptosis in the testis was assessed by histopathological examination, the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL) and flow cytometric examination of isolated spermatogenic cells stained with 7 aminoactinomycin D (7-AAD). Results: EMF exposure did not significantly affect the body and testis weights, but significantly increased the incidence of germ cell death. The distinguishing morphological feature of EMF exposure was a decrement in the number of well organized seminiferous tubules. Quantitative analysis of TUNEL-positive germ cells showed a significantly higher apoptotic rate in the 0.5  相似文献   

6.
Assessment of germ cell apoptosis in cryptorchid rats   总被引:8,自引:3,他引:5  
Aim: To investigate the relationship between germ cell degeneration and apoptosis in cryptorchid rats. Methods: Thirteen 21-day-old Wistar rats were made unilaterally cryptorchid by closing the left inguinal canal. At day 30 (Group 1, n=6) and day 60 (Group 2, n=7) after operation, the testes were removed for histopathological examination. The controls (n=8) were sham operated and were sacrificed at day 60. Germ cell apoptosis was assessed by means of the TUNEL method. Results: Spermatogenesis was arrested and the testicular and seminiferous tubular diameters were significantly reduced In the unilateral undescended testes (UUTs) compared with the contralateral descended testes (CDTs) and the control rats. However, atrophic changes, pathological calcification, necrosis of seminiferous tubule, and absence or sloughing of germ cells were not found in all the animals. The spermatocytes were the main type of germ cells undergoing apoptosis in all the groups. In the UUTs, there was a significant and time-depe  相似文献   

7.
Objective: To examine the expression of the tau protein and mi-crotubule-associated proteins (MAP) in the testicular interstitium of aged and young rats. Methods: Sprague-Dawley male rats were divided into a young group (6 months) and an aged group (28 months) of 10 animals each. The two-step immunohistochemistry method with the antibody against tau protein and MAPa was performed with the testis tissues. Results: The immunoreactive cells of the testicular interstilial tau protein were significantly increased (P<0.01) and those of the MAP significantly decreased (P<0.01) in the aged than in the young rats. Conclusion: The changes in the expression of the tau protein and MAP may be related to the aging process of the testis.  相似文献   

8.
目的 探讨大鼠隐睾中内皮型一氧化氮合酶(eNOS)和血管内皮细胞生长因子(VEGF)的表达与单侧隐睾对侧睾丸损害的关系.方法 将45只雄性SD大鼠(22 日龄)随机分成单侧隐睾并生殖股神经离断组(A组)、单侧隐睾组(B组)和假手术组(C组),每组15只.动物模型建立后(65日龄),苏木素-伊红(HE)染色观察睾丸生精上皮形态,原位缺口末端标记法(TUNEL)检测对侧睾丸生精细胞的凋亡,免疫组织化学和Western blot方法检测对侧睾丸组织中eNOS和VEGF基因表达的变化.结果 B组相对于A组和C组对侧睾丸组织中生精细胞的凋亡率最高(t1=3.04,t2=3.94,t1,t2>t28,P<0.01),Western blot和免疫组织化学方法检测结果也显示B组eNOS和VEGF的表达含量较A组和C组都显著升高,差异有统计学意义(P<0.01),而A组和C组的各指标差异均无统计学意义(P>0.05).结论 eNOS和VEGF的高表达和生殖股神经在单侧隐睾对侧睾丸的损害中起重要作用,而切断生殖股神经可以阻断这一损害过程.
Abstract:
Objective To study the relationship between the expression of endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF) with the damage of contralateral testis of unilateral cryptorchidism in the experimental rats. Methods Forty-five immature male Sprague-Dawley rats (aged 22 days) were randomly divided into the group A (unilateral cryptorchidism and the ipsilateral genitofemoral nerve division), group B (unilateral cryptorchidism), group C (sham operation), n = 15 in each group. When the rats were aged 65 days, all the rats were sacrificed and the testes were obtained. The morphological changes of the spermatogenic epithelium in the testes were observed, and the germ cell apoptosis was detected by the TdT-mediated dUTP-biotin nick end labeling (TUNEL) technique. The expression of eNOS and VEGF was detected by using Western blotting and immunohistochemistry in the testicular tissues.Results The germ cell apoptosis was increased significantly ( t1 = 3. 04, t2 = 3. 94, t1 ,t2 > t28 , P <0. 01) , and the levels of eNOS and VEGF in the contralateral testes were also increased obviously in group B as compared with groups A and C ( P < 0. 01) , but the entire indexes in groups A and C had no significant difference. Conclusion eNOS, VEGF and genitofemoral nerve play a important role in the damage of the contralateral testes of unilateral cryptorchidism, and the damage can be prevented by genitofemoral nerve division.  相似文献   

9.
Aim:To investigate the effect of cocaine on apoptosis and caspase-3 activity in germ cells in male rats at differentages.Methods:Cocaine hydrochloride was given(15 mg/kg body weight s.c.)to male Sprague-Dawley rats of3 weeks(n=8),6 weeks(n=8)and 12 weeks(n=8)of age,daily for 28 days.The serum levels of folliclestimulating hormone(FSH),luteinizing hormone(LH),prolactin(PRL),testosterone(T)and estrogen(E_2)wereassayed,and the DNA fragmentation of germ cells was determined by gel eletronphoresis.The cell cycle,apoptosisand caspase-3 activity of germ cells were tested by flow cytometry.Results:After the 28-day cocaine treatment,testes weight of the 3-week-old rats,the testes and body weights of the 6-week-old rats were decreased significantlycompared to those of their corresponding controls(P<0.05).The serum level of T was decreased significantly inthe 3-week-old and 6-week-old rats,and the serum level of PRL was also decreased significantly in 12-week-old ratscompared to the controls(P<0.05).In all the three cocaine-treated groups,the isolated DNA displayed a clear ladderpattern,especially in the 6-week old rats.The number of apoptosic germ cells increased significantly in 3-and 6-week-old rats treated with cocaine(P<0.05).The caspase-3 activity in all three groups increased significantlycompared to the controls(P<0.05),especially in the 6-week-old rats.Conelusion:Cocaine exposure for 28 daysleads to significant damage to male gonad and apoptosis elevation in testes of rats of different ages,especially in thoseof 6 weeks of age.The increase in caspase-3 activity might be a key pathway related to the early stage of apoptosisas the mechanism of cocaine-induced germ cell loss.(Asian J Androl 2006 Sep;8:569-575)  相似文献   

10.
Prepubertal boys treated for cancer may exhibit impaired fertility in later life. A number of chemotherapeutic agents have been identified as being gonadotoxic, and certain treatment regimens, such as that used for Hodgkin‘s disease, are particularly associated with subsequent infertility. Radiotherapy may also cause gonadal damage, most notably following direct testicular irradiation or total body irradiation. Because of the varied nature of the cytotoxic insult, it can be difficult to predict the likelihood of infertility in later life. Currently it is not possible to detect gonadal damage early due to the lack of a sensitive marker of gonadal function in the prepubertal age group. Semen cryopreservation is currently the only method of preserving fertility in patients receiving gonadotoxic therapy. This is only applicable to postpubertal patients and can be problematic in the adolescent age group. At present there is no provision for the prepubertal boy, although there are a number of experimental methods currently being investigated. By harvesting testicular tissue prior to gonadotoxic therapy, restoration of fertility could be achieved following treatment, either by germ cell transplantation or by in vitro maturation of the germ cells harvested.Alternatively, rendering the testes quiescent during cytotoxic treatment may protect the germ cells from subsequent damage. In addition to the many scientific and technical issues to be overcome prior to clinical application of these techniques, a number of ethical and legal issues must also be addressed to ensure a safe and realistic prospect forfuture fertility in these patients.  相似文献   

11.
This study evaluated the long term effects of unilateral torsion of the spermatic cord on the contralateral testis of guinea pigs, employing both fine structural and quantitative studies. Young, adult Hartley strain guinea pigs were divided into six experimental groups (12 animals per group). The first three groups consisted of 36 animals in which unilateral torsion was surgically induced. In group I (torsion maintained), unilateral torsion of the spermatic cord was maintained until the day of sacrifice; in group II (torsion and untwist), torsion of the spermatic cord was maintained for 8 to 12 hours, then the spermatic cord was untwisted and the testis was retained until the day of sacrifice. In group III (torsion and orchiectomy), testes were removed after 8 to 12 hours of spermatic cord torsion. The second three groups consisted of 36 animals: group IV (unilateral orchiectomy), group V (unilateral sham operation), and group VI (pentobarbital injection alone), which served as controls. One half of the animals from each group were killed after 4 months and the other half were killed after 8 months. The most frequently observed histologic changes in the contralateral testes of the experimental animals were focal disorganization and exfoliation of immature germ cells into the lumen. Severe damage, with almost complete absence of germ cells, was noted only in an occasional tubule. Quantitative evaluation of the germ cells of the contralateral testis revealed significant loss of germ cells in groups I, II, and III after 4 months, and in groups I and II after 8 months.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

12.
In our previous studies, we reported that short-term unilateral spermatic cord torsion had no adverse effect on the germ cells and the Sertoli cell in the contralateral testis of men. As an extension of our earlier investigations on the testicular pathophysiology in humans after unilateral spermatic cord torsion, the present study was undertaken to assess the Leydig cell function employing both fine structural and morphometric analysis in patients with short-term spermatic cord torsion. Bilateral testicular biopsy samples obtained from 4 men (15-19 years) with short-term unilateral torsion of the spermatic cord and from a control group of 6 men (15-40 years) were used in the present investigation. No appreciable difference in the Leydig morphology was noted between the biopsy samples from control and the contralateral testes. This was substantiated by morphometric analysis. The present study clearly indicates that patients with unilateral torsion of the spermatic cord may not essentially have bilateral testicular abnormalities, as suggested by the previous investigators. This report, thus lends further support to our earlier contention that alteration in microcirculation is quite likely the earliest and possibly the most significant contributor to the contralateral testicular damage in man after ipsilateral spermatic cord torsion.  相似文献   

13.
Unilateral spermatic cord torsion in the presence or absence of ipsilateral testis causes hypoxia in the contralateral testis. An experimental study was conducted to find the most important structure that causes contralateral testicular hypoxia following ipsilateral twisting. In five groups each consisting of 10 rats sham operations, epididymoorchiectomy, spermatic cord torsion, spermatic cord torsion following subepididymal orchiectomy or spermatic cord torsion following epididymoorchiectomy were performed. Lactic acid, hypoxanthine and thiobarbituric acid reactive products of lipid peroxidation (TBAR) were determined in the contralateral testis. While lactic acid, hypoxanthine and TBAR values did not differ significantly following sham and epididymoorchiectomy procedures, evaluation of other groups revealed significantly increased values compared with sham and epididymoorchiectomy groups. Since torsion of only spermatic cord and testicular vasculature causes contralateral testicular hypoxia, testis and epididymis do not seem to be mandatory for occurrence of contralateral testicular hypoxia. Testicular artery under distress seems to be the most important structure that results in contralateral testicular hypoxia following torsion.  相似文献   

14.
Torsion of the spermatic cord is not uncommon among young men. Various abnormalities in the histology of the contralateral testis have been reported due to unilateral torsion of the spermatic cord. We quantitatively estimated the germ cells from three groups of men: normal individual (Group I), men with unilateral torsion of short duration (Group II), and men with unilateral torsion of long duration or some other condition such as varicocele or intermittent torsion to the contralateral testis (Group III). No significant difference in the number of spermatogonia, spermatocytes, and spermatids of Groups I and II patients was observed. This observation indicates that there was no pre-existing morphophysiologic defect in the testis of Group II patients. Severe damage in the contralateral testis was noted in Group III patients. This indicates that if a damaged testis is retained in the body for a long time, the contralateral testis may be affected. Contralateral testis may also be affected by intermittent torsion or varicocele.  相似文献   

15.
Summary The object of the present investigation was to study the long-term effects of the unilateral torsion of the spermatic cord on the contralateral testis. Eighteen guinea pigs were divided into 3 groups. In group I of six animals, unilateral torsion of the spermatic cords was maintained until the time of sacrifice. In group II of six animals, torsion of the spermatic cords was maintained for 8–12h, then the spermatic cords were untwisted and the animals were maintained until the day of sacrifice. Group III six animals, received an injection of pentobarbital, which served as control. All animals were sacrificed after 16 months. Extensive light and electron microscopic studies were carried out. In the contralateral testes of the experimental group of animals, several degenerative changes were noted, which included excessive intraepithelial vacuolization, a loss of germ cells and the presence of tubules containing only Sertoli cells and a few spermatogonia. 10.6% and 19.5% seminiferous tubules were damaged in the contralateral testes of torsion maintained and the torsion reversed groups of animals, respectively in comparison to 3.1% tubular damage (indicated only by occassional presence of intraepithelial vacuoles and necrotic germ cells), in the control testis. It was concluded that long-term effect of unilateral torsion of the spermatic cord is permanent and irreversible in nature.  相似文献   

16.
大鼠一侧睾丸扭转对侧睾丸改变的实验研究   总被引:24,自引:1,他引:23  
目的 :研究一侧睾丸扭转 (UTT)后对侧睾丸组织学及生精细胞凋亡的改变 ,以明确UTT后对侧睾丸是否存在损伤。 方法 :SD雄性大鼠 6 0只 ,随机分为实验组 (n =4 8)及对照组 (n =12 )。实验组采用Turner方法建立左侧睾丸扭转模型 ,于扭转后 6h处死 4只 ,其余 4 4只再分为扭转睾丸复位及切除组 ,分别于术后 1d、1周、4周处死7~ 8只 ,取睾丸组织进行组织学及生精细胞凋亡的检测。 结果 :UTT复位后对侧睾丸组织学发生明显改变 ,生精细胞凋亡指数明显高于对照组 (P <0 .0 5 )。扭转睾丸切除后对侧睾丸变化不明显。 结论 :UTT可引起对侧睾丸损伤 ,其机制可能与再灌注有关 ,扭转睾丸切除可防止或减轻对侧睾丸的损伤  相似文献   

17.
OBJECTIVE: To determine the changes occurring during ipsilateral spermatic cord torsion either in the presence or absence of the ipsilateral testis and epididymis, by evaluating noradrenaline and nitrite-nitrate concentrations in the contralateral testes. MATERIALS AND METHODS: Forty male albino rats were allocated randomly to one of four equal groups undergoing: group 1, a sham operation; group 2, ipsilateral spermatic cord torsion; group 3, epididymo-orchidectomy only; and group 4, spermatic cord torsion after epididymo-orchidectomy. The contralateral testes were harvested after 24 h and the noradrenaline and nitrite-nitrate contents determined. The levels in each group were compared using the Kruskal-Wallis and Mann-Whitney U-tests. RESULTS: The noradrenaline content of testes from group 2 was significantly lower than in those of groups 1 and 3, but there were no significant differences in content between groups 1 and 3, 1 and 4, and 2 and 4. The content in group 4 was significantly less than that in group 3. There were no significant differences in nitrite-nitrate contents among any of the groups. CONCLUSION: Spermatic cord torsion for 24 h, either in the presence or absence of a testis and epididymis, significantly decreased the noradrenaline content in the contralateral testis. This finding supports the suggestion that the sympathetic system is activated by exposure to noradrenaline in the contralateral testis during ipsilateral spermatic cord torsion, with no dependency on the presence of a testis and epididymis. As the nitrite-nitrate concentrations were unaffected, nitric oxide seems to have no role in contralateral testicular deterioration.  相似文献   

18.
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.  相似文献   

19.
OBJECTIVE: Unilateral testicular torsion results with a decrease in contralateral testicular blood flow caused by a reflexive sympathetic response. The aim of this study was to investigate whether twisting of the spermatic cord, or testicular ischemia without twisting, activates this reflex mechanism and causes ultrastructural changes in the contralateral side. MATERIALS AND METHODS: Thirty adult male albino Wistar rats were randomly allocated into three groups of sham, torsion, and ligation. Right testes were twisted 720 degrees counterclockwise in the torsion group. Right spermatic cords were ligated permanently with a silk suture including the vas deferens in the ligation group. After 24 h of testicular ischemia, contralateral left testes were removed for electron microscopic evaluation. RESULTS: Contralateral testes showed similar ultrastructural changes in the torsion and ligation groups. The fibrous tunica propria enveloping the seminiferous tubule was thickened due to increased collagen fibers. The basal lamina was continuous but thickened and showed several foldings. The gap between basal lamina and the germ cells was increased because of collagen fibers. Leydig cells showed mitochondrial degeneration with the loss of its cristae. Leydig cells lost their contact with its neighborhood cells in some areas, and these gaps were filled with collagen fibers. Germ cells showed dilated cisternae of smooth endoplasmic reticulum, cytoplasmic electron-dense bodies and clear regions. CONCLUSIONS: Similar electron microscopic findings observed in the torsion and ligation groups indicate that testicular ischemia rather than twisting of the spermatic cord is responsible for the ultrastructural changes in the contralateral side.  相似文献   

20.
Although deteriorating effects of unilateral spermatic cord torsion are generally accepted, the mechanism remains controversial. An experimental study was performed to evaluate the necessity of testicular and spermatogenetic material for contralateral testicular deterioration following unilateral spermatic cord torsion in rats. The animals were allocated to four groups: control, spermatic cord torsion, subepididymal orchiectomy, and spermatic cord torsion 14 days after subepididymal orchiectomy. The testes were removed on the 14th days and mean seminiferous tubular diameters and mean testicular biopsy scores were determined. Although contralateral testicular deterioration was more pronounced in the presence of testicular tissue, the absence of testicular tissue and/or spermatogenetic material did not prevent its occurrence. This is highly suggestive that autoimmune mechanism does not play a role in contralateral testicular damage following unilateral spermatic cord torsion.  相似文献   

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