L-肉碱在奥硝唑所致大鼠睾丸和附睾损伤中的保护作用

目的:探讨L-肉碱(LC)在奥硝唑(ORN)所致大鼠附睾和睾丸损伤中的的保护作用。方法:40只雄性SD大鼠(200～230g)随机均分为5组:①A组:给予0.5%的羧甲基纤维素钠(溶剂)灌胃;②B组:每天给予400mg/kgORN灌胃;③C组:每天给予800mg/kgORN灌胃;④D组:每天给予[ORN(400mg/kg)+LC(100mg/kg)]灌胃;⑤E组:每天给予[ORN(800mg/kg)+LC(100mg/kg)]灌胃。上述各组均连续灌胃20d,末次给药24h后,所有大鼠麻醉后处死,分别取睾丸、附睾,进行称重和HE染色,计算睾丸、附睾系数并观察睾丸和附睾病理组织学改变。结果:①与A组相比,B组睾丸、附睾系数明显降低(P<0.05);而C组睾丸、附睾系数为极显著性降低(P<0.01);D组与A组相比无差异,E组与A组相比有极显著性差异(P<0.01);②HE染色显示,与A组相比,B组睾丸生精小管内各级生精细胞排列基本整齐,部分生精小管管腔内有脱落的生精细胞,附睾管腔中精子数目下降,有时可见散在的生精细胞;C组大鼠睾丸生精小管管腔内均可见坏死脱落的生精细胞,附睾管腔中精子数目明显减少,且有较多的非精子细胞成分。D组睾丸生精小管无明显改变,附睾管腔中精子数目也未见明显下降;E组睾丸生精小管管腔内精子数目减少,可见坏死脱落的生精细胞,附睾腔中精子数目明显减少,并伴有较多的非精子细胞成分。结论:奥硝唑(ORN)可导致雄性大鼠附睾和睾丸病理组织学改变,LC对ORN引起大鼠附睾和睾丸损伤具有一定的保护作用。     

Effect of lead chloride on spermatogenesis and sperm parameters in mice

Aim: To evaluate the effect of acute lead chloride exposure on testis and sperm parameters in mice.Methods: PbC12, 74 mg/kg, was daily administered to sexually mature male mice for 3 days and the effects on the testicular histology and ultrastructure as well as the motility and density of spermatozoa in cauda epididymis were observed. An additional group of mice were treated for 1-3 days and were allowed to recover for 32 days to determine the reversibility of lead-induced changes. Results: The testicular weight, seminiferous tubular diameter and sperm counts were significantly decreased following 3 days of PbCl2 treatment, but were unaffected by shorterterm exposures. The changes caused by lead are mostly reversible. Conclusion: Acute lead chloride exposure injures the fertility parameters of male mice and the effects are partially reversible. (Asian JAndrol 2004 Sep; 6: 237-241)     

Ontogeny and cellular origin of an interleukin-1 -like factor in the reproductive tract of the male rat

We have recently isolated an interleukin-1 (IL-1)-like factor from the rat testis, which originates from the seminiferous tubules and is a protein with an MW of 17,000 and a pI of 5-6. This paper reports on the appearance of the IL-1-like factor during postnatal development and investigates its cellular origin further. IL-1 activity was measured by a murine thymocyte proliferation assay. Very low IL-1 activity was present in culture medium conditioned by seminiferous tubules from rats aged 10 or 20 days. From 30 days of age, increasing amounts were detected, reaching a maximum level in adult animals (60-90 days). No IL-1 activity was found in medium conditioned by peritubular cells. Sertoli cell-enriched seminiferous tubules obtained from experimentally cryptorchid or from prenatally irradiated rats produced much higher levels of IL-1 activity than did those obtained from intact testes. IL-1 activity was detected in efferent duct fluid after ligation of the efferent ducts for 24 h, indicating that the IL-1-like factor was secreted into the tubular lumen. Low levels of IL-1 activity were detected in extracts of epididymal tissue and epididymal sperm, whereas ejaculated seminal plasma, seminal vesicle fluid and extracts of seminal vesicles (together with the coagulating glands) and ventral and dorsolateral prostate lacked IL-1 activity. Instead, seminal plasma inhibited testicular IL-1 activity dose-dependently without affecting cell viability in the thymocyte cultures. Although its biological function remains to be defined, our results indicate that the testicular IL-1-like factor is produced by Sertoli cells and that its appearance during development coincides with the initiation of active spermatogenesis in the rat testis.     

Protection of spermatogenesis against gamma ray-induced damage by granulocyte colony-stimulating factor in mice

The radioprotective effects of granulocyte colony-stimulating factor (GCSF) were further investigated with respect to the testicular system. Recombinant human GCSF (100 μg kg(-1) body weight/day) was administrated to male C3H/HeN mice by subcutaneous injection for three consecutive days before pelvic irradiation (5 Gy) and histopathological parameters were assessed at 12 h and 21 days post-irradiation (pi). The GCSF protected the germ cells from radiation induced- apoptosis (P < 0.01 vs. irradiated group at 12 h pi). GCSF remarkably attenuated radiation-induced reduction in testis weight, seminiferous tubular diameter, seminiferous epithelial depth and sperm head count in the testes (P < 0.05 versus irradiated group at 21 days pi). Repopulation index and stem cell survival index of the seminiferous tubules were increased in the GCSF-treated group when compared with the radiation group (P < 0.01). The frequency of abnormal sperm in the GCSF group was lower than that in the irradiated group at 21 days pi (P < 0.01). The decrease in the sperm count and in sperm liability in the epididymis caused by irradiation was counteracted by GCSF. The present study suggests that GCSF protects from radiation-induced testicular dysfunction via an anti-apoptotic effect and recovery of spermatogenesis.     

Human chorionic gonadotropin deteriorates the histology of rat testes

OBJECTIVES: It is not yet certain whether early hormonal treatment in cryptorchidism is safe for germ cells. We investigated the histologic effects of human chorionic gonadotropin (hCG) therapy on descended testes of rats. DESIGN AND SETTING: Thirty male Wistar albino rats were randomized into two groups. The rats of the hCG group (n=15) were administered 50 IU/kg/day hCG once daily via the subcutaneous route for 15 days. Fifteen rats received subcutaneous isotonic saline and acted as controls. At the first month, testicular tissue was obtained after scarification in both groups. The histological examination was performed to evaluate the seminiferous tubular diameter, germinal membrane thickness, and the percentage of the open seminiferous tubule lumen in each testis to compare the two groups. RESULTS: The percentage of the open seminiferous tubular lumen in testicular tissues of hCG-treated rats was higher than that of controls (p<0.05). The mean germinal membrane thickness in testicular tissues of the hCG group was statistically lower than that of the control group (p<0.05). There was no statistical difference between mean seminiferous tubular diameter in testicular tissues of hCG-treated rats and controls, as expected (p>0.05). Additionally, there were two interesting cases of Sertoli cell only appearance in the hCG group. CONCLUSIONS: We may assume that hCG impairs the seminiferous tubule histology in normal testes of rats. Thus, further experimental studies on dose dependency and the reversibility of these effects are warranted.     

Effect of tamoxifen on spermatogenesis and tubular morphology in rats

Aim: To observe the effect of tamoxifen citrate on spermatogenesis and tubular morphology in rats. Methods: The effect of tamoxifen citrate i.g. at doses of 400 and 800 mg·kg·day-1 in 0.1 mL olive oil for 30 days on seminiferous tubular morphology, seminiferous epithelial diameter (STD), epithelial height (SEH), epididymal sperm count and percent abnormal sperm were evaluated at day 1, 12 and 36 after treatment. Controls were given the vehicle. Results: The higher dose resulted in tubular atrophy on day 31. The STD, SEH and sperm count were decreased and the abnormal spermatozoa increased in a dose-dependent manner with the maximal effect on day 36. Conclusion: Tamoxifen citrate induces tubular shrinkage and atrophy and sperm abnormality at a dose-dependent manner.     

Low sperm recovery from the undescended testis with testicular sperm extraction in postpubertal cryptorchids: preliminary report

As postpubertal cryptorchid testes are generally atrophic and have high malignancy risk, orchiectomy is recommended as the treatment method. However, a few case reports advocated orchiopexy due to finding sperm afterwards. The present clinical study aimed at determining the possibility of finding spermatozoa in postpubertal cryptorchid testis with testicular sperm extraction (TESE). Initially testicular biopsy and later TESE was performed in the undescended testis of 22 unilateral postpubertal cryptorchids and in one of the testes of three bilateral postpubertal cryptorchids. Histopathological assessment of testicular biopsy specimen showed that three patients had maturation arrest and 22 had seminiferous tubular atrophy. By TESE, spermatozoa were found in only one specimen of 25 testes. Our results show that the expectancy to find spermatozoa in postpubertal cryptorchid testis is extremely low by current sperm recovery methods and orchiectomy is still the accurate method of treatment.     

Acute effects and long-term sequelae of 1,3-dinitrobenzene on male reproduction in the rat. I. Sperm quality, quantity, and fertilizing ability

Groups of eight adult male rats were given a single oral dose of 0 or 48 mg/kg of 1,3-dinitrobenzene and sacrificed at 1, 2, 4, 8, 16, 24, 32, 72, and 175 days posttreatment. The groups killed at 175 days were bred to untreated females during weeks 3, 4, 6, 9, 13, and 24. Decreased testis weight and testicular sperm numbers were observed by day 4; decreased cauda sperm reserves and epididymis weight occurred by day 8 and day 16, respectively. Reduced numbers of motile spermatozoa and abnormal sperm morphology were seen in spermatozoa from the cauda epididymidis by day 16. Fertilizing ability, as indicated by the presence of two pronuclei and a sperm tail in eggs flushed from the oviducts of inseminated females, was slightly reduced by week 4 and declined to zero by week 6. Group means for reproductive organ weights, sperm production, and sperm reserves failed to return to control levels although some individual animals approached full recovery. Normal fertilizing ability was restored in most animals by week 13, but two of seven remained infertile. Occlusion of some efferent ductules was observed in three of seven animals at 175 days. This study indicates that 1,3-dinitrobenzene is a potent testicular toxicant in the rat, capable of producing marked testicular damage, infertility, and possibly sterility from a single exposure.     

The natural course of cryptorchidism in rats and the efficacy of orchidopexy or orchidectomy in its treatment before and after puberty.

Both clinical and experimental evidence suggest that fertility is impaired in unilateral cryptorchidism. To investigate the effect of the undescended testis on the contralateral descended gonad, a new experimental model based on natural cryptorchidism in rats was designed. Seventy male Buffalo rats with an undescended right testis noted at the age of 30 days were used. Fifty healthy animals served as a controls. The natural course of cryptorchidism was investigated at the ages of 30, 90, and 180 days. The effects of orchiopexy and orchiectomy performed in cryptorchid animals before and after puberty were evaluated at the age of 180 days. Both nonoperated and operated animals were mated at the age of 150 days in order to estimate their fertility. The animals were killed at 30, 90, and 180 days of life and the testes were removed. In each excised testis testicular weight and seminiferous tubular diameters were measured and the maturity of the germinal epithelium was determined using the Johnsen testicular biopsy score. The experiment demonstrated reduced testicular weight and seminiferous tubular diameters in undescended testis already at 30 days and arrest of spermatogenesis at the spermatocytes stage at 90 and 180 days. There was no significant difference between contralateral descended testes and controls at the age of 30 and 90 days, but at 180 days the degenerative changes were identical with those in the cryptorchid testes. Cryptorchid rats were completely infertile. Both orchiopexy and orchiectomy prevented the damage to the contralateral testis. A significant improvement in size and spermatogenesis was recorded in most cases of the surgically descended testes.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effects of human chorionic gonadotrophin on normal testicular tissue of rats: dose-dependence and reversibility

OBJECTIVE To investigate the effect of human chorionic gonadotrophin (hCG) on rat testicular tissue, and its reversibility and dose dependence. MATERIALS AND METHODS Male Wistar rats were assigned to groups (10 rats/group) receiving 10, 30 or 50 IU/kg hCG subcutaneously once daily for 15 days; 10 controls received subcutaneous isotonic saline. At 1 and 3 months later, five rats in each group were killed and their testes removed. The testes were examined histologically to measure seminiferous tubular diameter and germinal membrane thickness. RESULTS At 1 month after hCG administration, the mean germinal membrane thickness in the testicular tissues of the hCG-treated rats was significantly less than in control rats, and was also significantly different between all of the hCG-treated groups (P < 0.05). However, at 3 months after hCG administration, all histological variables were similar to those in control rats (P > 0.05), and the mean germinal membrane thickness at 3 months after hCG administration was larger than that at 1 month (P < 0.05). There were no significant differences in the mean seminiferous tubular diameter between hCG-treated rats and control rats. CONCLUSION hCG impairs seminiferous tubule histology in the 'normal' descended testes of rats. This effect was dose-dependent, and the changes were reversed at 3 months after treatment. Thus, although hCG therapy might affect the seminiferous tubules of contralateral descended testes in cryptorchid boys, these effects might be reversible.     

氰戊菊酯对雄性大鼠生殖内分泌系统的影响

目的 :研究氰戊菊酯 (Fen)对雄性生殖内分泌系统的损害作用及其机制。　方法 :将不同剂量的Fen(0、2 .4、12、6 0mg/kg) ,每日分别对雄性成年SD大鼠连续灌胃 ,染毒 15、30d ,应用RIA法测定大鼠血清中FSH、LH、T和睾丸匀浆中T的水平 ,同步测定睾丸标志酶ACP、γ GT的活性 ,并采用精子头计数法观测每日精子生成量 (Spr)的变化。　结果 :与对照组相比 ,染毒 15d时 ,血清中FSH水平在≤ 12mg/kg剂量组均明显升高 (P <0 .0 1) ,血清中LH含量在 12mg/kg剂量组显著增加 (P <0 .0 1) ,而睾丸匀浆中T在≥ 12mg/kg剂量组中表现为显著下降 (P<0 .0 1) ;染毒至 30d时 ,血清中FSH水平在≥ 12mg/kg剂量范围继续呈现显著增加 (P <0 .0 1) ,睾丸匀浆中T在2 .4mg/kg剂量组则降低 (P <0 .0 5 )。ACP活性在染毒 15d时 2 .4mg/kg剂量组表现为升高 (P <0 .0 5 ) ,继续染毒至 30d时 6 0mg/kg剂量组则显著减低 (P <0 .0 5 ) ;γ GT活性则始终随染毒剂量的增加而降低 (P <0 .0 5 )。Spr与染毒剂量有明显的剂量依赖关系 ,在≥ 12mg/kg剂量范围显著减少 (P <0 .0 1)。 　结论 :Fen对雄性大鼠有明显的生殖毒性 ,可影响其血清及睾丸性激素水平和酶活性 ,这可能与Fen对支持细胞和生精上皮的损害有关     

Serum reproductive hormone levels and sperm production in male adult rats after treatment with arresting, a fraction obtained from seminiferous tubules conditioned medium

This study used seminiferous tubule (ST) segments from adult rats to condition culture medium that had been concentrated, size fractioned and administered 10-84 days to adult rats by subcutaneous or intratesticular injection and the effects on testes weight, testosterone, luteinizing hormone (LH) and FSH levels and (homogenization-resistant) epididymal sperm count were determined. The conditioned medium obtained 2 days after culture of ST was fractionated in a 30-100 kDa component. The fraction was injected subcutaneously or intratesticularly. This factor(s), named arresting, decreases sperm count in the epididymis from 13 days to 84 days of treatment without changes in serum LH or testosterone levels. The results of the present study suggest that arresting acts on spermiogenesis/spermiation and/or the entry of sperm into the epididymis from the efferent ductules.     

The effects of ethylene glycol monomethyl ether on testicular histology in F344 rats

Ethylene glycol monomethyl ether (EGME) has been found to produce testicular atrophy in experimental rodents. The studies that follow were designed to determine the testicular cell type(s) most susceptible to EGME administration. For histologic studies, F344 rats were gavaged with 150 mg/kg/day of EGME 5 days per week, and serially sacrificed. In sections from perfusion-fixed tissue, necrotic changes were observed in some meiotic and premeiotic spermatocytes 24 hours after a single dose. Also, nuclear condensation was seen in occasional early pachytene spermatocytes. These effects were magnified after two doses; there were more necrotic pachytene and meiotic spermatocytes than necrotic stage I pachytene spermatocytes. By day 4, testes from all treated animals were affected; there was a pronounced maturation-depletion effect, seen as the absence of round spermatids from tubules in stages I to III. These effects continued to develop at days 7 and 10, leaving only Sertoli cells, spermatogonia, and late stage spermatids populating the epithelium. Other animals were treated similarly, but subject to efferent duct ligation 16 hours prior to sacrifice. Fluid production, as judged by weight gain in the testes after efferent duct ligation, was unaffected by EGME treatment. Analysis of the fluid collected at the rete testis indicated that there was no treatment-related change in the relative amounts of androgen binding protein. The data indicate that the spermatocyte is the primary target cell for the histologic effects of EGME in the testis of F344 rats.     

Morphologic changes in efferent ductules and epididymis in estrogen receptor-alpha knockout mice

Estrogen has been shown to have an important role in fluid reabsorption in efferent ductules of the testis. Our previous study of the estrogen receptor-alpha knockout mouse (ERKO) showed that the efferent ductules and rete testis were primary targets of estrogen receptor function. In the present study, a more comprehensive evaluation of the ERKO male reproductive tract was performed to determine the severity of effects in efferent ductules as well as the epididymis. The following observations were found in ERKO males: 1) blind-ending efferent ductules were more prevalent in ERKO than in wild type (WT) tissues; 2) glycogen-containing cells were observed at the rete testis-efferent ductule junction; 3) the tubular diameters of the efferent ductules and initial segment epididymides were dilated; 4) efferent ductules were dilated between 130 to 300% over wild type ductules; 5) efferent ductule epithelial height was reduced nearly 50%; 6) microvilli of nonciliated cells of efferent ductules were 64% shorter in length; 7) cilia were reduced in number; 8) initial segment epithelium was displaced into regions adjacent to the rete testis and in short segments of the common region of efferent ductule; 9) apical, narrow, and clear cells of the epididymis also were abnormal in some regions; 10) in the corpus and cauda regions, sperm granulomas were noted in one third of the ERKO males. In conclusion, the entire reproductive tract is affected in ERKO males. The cells showing the greatest effects were estrogen receptor-positive cells. It appears that in the ERKO mouse there are developmental anomalies that must be considered separately from adult dysfunctional changes in the male reproductive tract.     

6‐Gingerol‐rich fraction prevents disruption of histomorphometry and marker enzymes of testicular function in carbendazim‐treated rats

Previous investigations demonstrated that 6‐gingerol‐rich fraction (6‐GRF) prevented testicular toxicity via inhibition of oxidative stress and endocrine disruption in CBZ‐treated rats. The influence of 6‐GRF on alterations in histomorphometry and marker enzymes of testicular function in CBZ‐treated rats which hitherto has not been reported was investigated in this study. The animals were orally administered either CBZ (50 mg/kg) alone or in combination with 6‐GRF (50, 100 and 200 mg/kg) for 14 consecutive days. Histomorphormetric analysis demonstrated that 6‐GRF significantly prevented CBZ‐mediated increase in the organo‐somatic index of the testes and seminiferous tubular diameter as well as the reduction in epithelium height and tubular length of testes in the rats. Similarly, 6‐GRF ameliorated CBZ‐induced disruption in the epithelium height as well as in the proportion of tubule and interstitium of the epididymis the treated rats. Furthermore, 6‐GRF prevented CBZ‐mediated increase in testicular acid phosphatase activity and the decrease in testicular alkaline phosphatase, aminotransferases, glucose‐6‐phosphate dehydrogenase and lactate dehydrogenase activities. Moreover, 6‐GRF ameliorated CBZ‐induced reduction in the testicular and epididymal sperm count and sperm motility in the treated rats. Conclusively, 6‐GRF enhances key functional enzymes involve in spermatogenesis and maintains histo‐architecture of testes and epididymis in CBZ‐treated rats.     

Effects of acute and chronic doses of methoxy acetic acid on hamster sperm fertilising ability

Aim: To evaluate the effects of acute and chronic doses of methoxy acetic acid (MAA) on in vitro fertilisation by hamster sperm and to correlate the data with the testicular damage. Methods: Adult male hamsters were gavaged with 3 single doses (0, 80, 160 and 650 mg/kg) and 3 chronic doses (0, 8, 32 and 64 mg/kg daily for 5 weeks) of MAA in distilled water. After treatment hamsters were killed at weekly intervals and spermatozoa recovered from the distal cauda epididymides were used to assess the fertilising capacity in vitro. The testes were processed for histological examination. Results: Acute doses showed a significant reduction in sperm fertilising ability from week 3 and 4 after treatment and with the chronic doses, the effects were more extensive and persistent. The results were in correpondence with the testicular damages observed. Conclusion: It is evident that both acute and chronic doses of MAA can impair the sperm function by damaging one or more cell populations in the testis.     

Obstruction of the tubuli recti and ductuli efferentes by dilated veins in the testes of men with varicocele and its possible role in causing atrophy of the seminiferous tubules

Hormone measurements, spermiograms and testicular biopsies studies were performed in young with varicocele. In addition, the testes and epididymides of 27 adults with varicocele were obtained from autopsies. Light and electron microscopic examination of biopsy and autopsy specimens revealed two types of lesions in testes with varicocele: 1) a diffuse lesion consisting of abnormal spermatozoa and spermatid morphology and sloughing of immature spermatozoa and spermatid; 2) focal lesion, distributed irregularly throughout the testicular parenchyma, affecting several small groups of seminiferous tubules. Each of these groups corresponded to a testicular lobule and showed different degrees of tubular atrophy, so that the focal lesions were distributed in a mosaic pattern. The testicular interstitium showed dilated veins and venules, and progressive collagenization. Some testes showed dilated veins in the rete testis, which compressed several tubuli recti and caused tubular atrophy in the seminiferous tubules opening into these tubuli recti. Other testes showed dilated young veins among the ductuli efferentes, and the rete testis channels appeared to be dilated. Among the different etiological mechanisms which have been suggested to for testicular lesions in varicocele, tubular obstruction at the level of either the tubuli recti or the ductuli efferentes might be responsible for lesions leading to testicular atrophy.     

Acute experimental testicular torsion. No effect on the contralateral testis

Other investigators have shown that chronic unilateral testicular torsion produces negative effects on the contralateral testis in experimental animals. In the present study, bilateral testicular weight and histology, and concentrations and motility of spermatozoa from the cauda epididymidis were studied after 0 to 4 hours of acute unilateral testicular torsion in the rat. The obstruction of blood flow by torsion was documented, as well as the presence or absence of return blood flow after the relief of torsion. The above mentioned parameters of testicular function were studied at 7, 30, and 60 days after relief of torsion. Ipsilateral testis weights and epididymal sperm concentrations and motility were significantly reduced by 1, 2, and 4 hours of torsion. The histology of torsioned testes was also severely altered, and no seminiferous epithelial repair was evident 60 days after torsion. Contralateral testicles were not affected by ipsilateral torsion of 1, 2, or 4 hours duration, despite the fact that the ipsilateral testis function was completely compromised by 2 and 4 hours of torsion. These results indicate that there would be no clinical benefit in removing the acutely torsioned testis of Sprague-Dawley rats since it poses no threat to the contralateral testis.     

青春期前邻苯二甲酸二丁酯持续暴露对大鼠睾丸发育的影响

目的:研究青春期前邻苯二甲酸二丁酯(DBP)持续暴露对睾丸发育的影响。方法:21日龄断乳青春期前雄性SD大鼠随机分为对照组(n=24)和实验组(n=54),每日分别用玉米油或DBP玉米油溶液灌胃,DBP暴露剂量分别为50mg/(kg.d)(低剂量组,n=18)、200mg/(kg.d)(中剂量组,n=18)和600mg/(kg.d)(高剂量组,n=18),各组动物持续暴露14、21、28d后(即PND35,PND42和PND49)断颈处死。记录大鼠体重变化,检测睾丸重量和体积、附属性器官重量及附睾精子,化学发光免疫分析法检测血清睾酮含量,苏木精-伊红染色观察睾丸组织形态学变化,测量生精小管平均直径及进行睾丸活检评分。结果:低剂量组PND35少量生精小管生精细胞排列紊乱,PND42和PND49睾丸、附属性器官发育及生精功能正常;中剂量组PND35和PND42生精细胞排列紊乱、数目减少,PND49生精小管内可见各级生精细胞及精子,睾丸未见萎缩,附属性器官发育正常;高剂量组大鼠体重增长减缓,血清睾酮水平低下,睾丸生精小管变性萎缩,生精上皮发育阻滞,生精细胞大量凋亡坏死,青春期大鼠睾丸萎缩,无精子,附睾、前列腺和精囊等附属性器官发育迟缓。结论:青春期前DBP持续暴露可损害睾丸组织发育和正常生精功能形成,其毒性效应具有剂量依赖性,高剂量DBP持续暴露引起的睾丸毒性在青春期前发育过程中不可修复,而低中剂量暴露引起的睾丸毒性在PND49之前可完全或部分逆转性恢复。     

Cisplatin-induced long-term failure of spermatogenesis in adult C57/Bl/6J mice

Exposure to cisplatin results in impaired spermatogenesis, azoospermia, and, sometimes, permanent infertility in male patients. The mechanism(s) by which cisplatin induces damage to testicular cells is poorly understood. We previously reported that acute exposure to cisplatin results in elevated germ cell apoptotic rates and that this indicates long-term damage to the seminiferous epithelium. Here, we present data that implicate an injury to Sertoli cells as a possible mechanism to explain an elevated rate of germ cell apoptosis and consequent infertility. Normal adult C57/Bl/6J mice were exposed to 1, 2, or 4 rounds of 1, 2.5, or 5 mg/kg cisplatin in a regimen designed to resemble clinical chemotherapeutic exposure (1 injection daily for 5 days with a recovery phase of 16 days between cycles). A dose-dependent reduction in testicular weight due to germ cell loss was observed. While exposure to 1 mg/kg caused only temporary germ cell depletion, higher doses (2.5 and 5 mg/kg) revealed widespread testicular atrophy as evidenced by gaps in the epithelium due to cytoplasmic vacuolization and loss of differentiating germ cells. Although the acute loss of germ cells by apoptosis can result in temporary infertility, the testis has the ability to repopulate itself with mature cells, provided the stem germ cell population remains unharmed. Here, we demonstrate that a sustained disruption of spermatogenesis occurs despite the continued presence of stem spermatogonia in the seminiferous epithelium. These results suggest that cisplatin-induced germ cell loss may occur, in part, as a result of Sertoli cell injury-dependent alterations in germ cell microenvironment.