Obesity adversely affects the outcome of antireflux operations

BACKGROUND: We hypothesized that obesity was associated with long-term failure of antireflux procedures, and that in obese patients antireflux operations were easier to perform via thoracotomy, and therefore likely to have a higher success rate than transabdominal (laparoscopic or open) antireflux procedures. The aims of this study was to determine the impact of obesity on the success of antireflux operations, and to compare the success rates of transthoracic and laparoscopic approaches in obese patients with gastroesophageal reflux. METHODS: The records of 224 consecutive patients undergoing antireflux surgery by two surgeons in a university-based tertiary care center were reviewed and patients contacted for follow-up assessment. The patients were classified into groups based on the type of operation performed and the calculated body mass index (BMI): normal (BMI 30). Recurrences were documented by symptoms responsive to acid-suppressive medication and radiologic or pH probe studies. RESULTS: Among the 224 patients included in this study, 187 underwent laparoscopic Nissen fundoplications (LNF) and 37 underwent Belsey Mark IV(BM4) procedures. The mean follow-up period was 37 months. The three groups included 89 (39.7%) patients classified as having normal weight, 87 (38.8%) as overweight and 48 (21.4%) as obese. Normal, overweight, and obese patients were similar in terms of age, gender, hiatal hernia size, degree of esophagitis, and comorbid conditions. A total of 26 recurrences occurred, giving an overall recurrence rate of 11.6%. There were 4 recurrences in the normal group (4.5%), 7 in the overweight group (8.0%; p not significant vs normal), and 15 in the obese group (31%; p < 0.001 vs normal; p <.001 vs overweight). The recurrence rate was similar between LNF and BM4 in each BMI subgroup, although in aggregate, the recurrence rate after BMW was greater than after LNF (10/37 vs 16/187; p < 0.02). CONCLUSIONS: Obesity adversely affects the long-term success of antireflux operations. Although athoracotomy provides optimal exposure of the hiatal structures in obese patients, a transthoracic approach was associated with a higher recurrence rate than LNF. Given the high failure rate of antireflux operations in obese patients, intensive efforts at sustained weight loss should be made before consideration of surgery.     

微波长期辐射对雄性生殖的影响研究

目的:探讨微波长期辐射对雄性大鼠生殖的影响。方法:100只二级雄性Wistar大鼠经平均功率密度为0、2.5、5和10 mW/cm2微波辐射4周(5次/周、6 min/次),于辐射后6 h、7 d、14 d、28 d和60 d,动态观测血清睾酮,睾丸指数、组织学和超微结构及附睾精子畸形率的变化。结果:2.5、5 mW/cm2微波辐射28 d[(10.20±4.31))ng/ml,(5.56±3.47)ng/ml]和10 mW/cm2辐射后28 d[(7.53±4.54)ng/ml]及60 d[(15.95±9.54)ng/ml]血清睾酮浓度较对照组[(23.35±8.06)ng/ml,(31.40±9.56)ng/ml]明显降低(P<0.05或P<0.01);3种剂量微波辐射后6 h～60 d,睾丸指数未见明显变化,但均出现不同程度生精细胞变性坏死脱落、生精上皮变薄、精子减少或缺失等改变,以辐射后28 d及60 d明显;5 mW/cm2辐射后7 d和60 d,超微结构见各级生精细胞线粒体肿胀、空化,精原细胞和Leydig细胞染色质凝集边移;附睾精子畸形率均呈增加趋势,其中2.5 mW/cm2辐射后7 d,5 mW/cm2辐射后60 d,10 mW/cm2辐射7 d、28 d、60 d附睾精子畸形率明显增加(P<0.01或P<0.05)。结论:微波长期辐射可引起雄性大鼠生殖损伤,与辐射剂量呈正相关,并具有明显的远后效应。     

Warfarin‐induced vitamin K deficiency affects spermatogenesis in Sprague‐Dawley rats

Vitamin K is present in the testes though its actual function in male reproduction is poorly understood. This study investigated the harmful effect of extrahepatic vitamin K insufficiency on the testicular structure. Sprague‐Dawley rats were fed with a diet containing warfarin for 2, 4 and 8 weeks; control animals received a standard diet without warfarin. It was found that extrahepatic vitamin K deficiency that is induced by warfarin results in histopathological features that range from delayed spermiation, presence of multinucleated giant cells in the seminiferous tubules, germ cells degeneration, asthenozoospermia, oligozoospermia and increase in the percentage of abnormal sperm morphology when compared to the controls. Data obtained from the two groups were analysed using the Student t test. It is concluded that warfarin‐induced vitamin K deficiency has a negative impact on spermatogenesis.     

Effects of the chronic use of finasteride on testicular weight and spermatogenesis in Wistar rats

OBJECTIVE: To evaluate spermatogenesis in rats chronically exposed to finasteride, as the recent use of finasteride in young men to prevent hair loss has raised concerns about chronic use and fertility. MATERIALS AND METHODS: Male Wistar rats (4 months old) were selected and divided into two groups. Group 1 (17 rats) received a finasteride suspension of 2 mg/kg/day in saline solution, 5 days/week for 10 months; group 2 (eight rats of the same age) were treated with placebo for the same period. At the end of the exposure the testes were weighed and processed for histological analysis. Spermatogenesis was evaluated as the mean number of seminiferous tubules with and without spermatozoids in their lumen, in five random fields on the same slide. Student's t-test was used to assess differences in the groups. RESULTS: In group 1, the mean (sd) weight of the testes was 1.55 (0.29) g and in group 2 1.58 (0.34) g (P>0.05). The histological analysis showed a mean of 13.35 (1.66) seminiferous tubules per field and 1.20 (3.30) tubules with no spermatozoids in group 1; in group 2 the respective values were 13.53 (1.46) and 0.06 (0.14) (P>0.05). CONCLUSION: Finasteride had no detectable effects on the quantitative and qualitative analysis of spermatogenesis in rats.     

雷公藤多甙抑制大鼠精子发生的研究

目的探讨雷公藤多甙对大鼠精子发生的抑制作用及其可能的信号通路。方法成年雄性大鼠给予雷公藤多甙(16 mg/kg)灌胃,每日1次,在2及6周检测血清睾酮(T)、卵泡刺激素(FSH)、黄体生成素(LH)和可的松水平;光镜观察睾丸组织的形态学变化;原位末端标记法(TUNEL)观察睾丸生精细胞凋亡;免疫组织化学法观察凋亡通路相关蛋白Bax/Bcl-2的表达。结果给药组与对照组相比,性激素、肾上腺皮质激素均无显著变化(P均>0.05);给药2周后精子数下降和畸形率上升(P<0.05),给药4和6周精子数下降和畸形率升高更显著(P<0.001);组织学检查给药组大鼠生精小管内各级精母细胞和精子细胞数明显减少,生精细胞排列紊乱,原始精原细胞和支持细胞(Sertoli细胞)未见明显改变。与正常对照组相比,生精小管内生精细胞凋亡显著增加(2周P<0.05,4和6周P<0.001)。凋亡相关蛋白Bax表达明显上调,Bcl-2表达无显著差异。结论雷公藤对大鼠精子发生的抑制作用表现为增加生精细胞凋亡,导致精子计数下降,精子的畸形率升高。雷公藤多甙使睾丸Bax表达增加,与诱导生精细胞凋亡相关,可能是相关的信号通路之一。进一步研究雷公藤多甙作用的分子信号机制有助于今后降低剂量、减少毒副作用,探讨其作为一种安全的男性避孕药可能性。     

Long-term effects of triptolide on spermatogenesis, epididymal sperm function, and fertility in male rats

Prior studies had suggested that triptolide, a diterpene triepoxide isolated from a Chinese medicinal plant, might be an attractive candidate as a post-testicular male contraceptive agent. Despite the promise that triptolide would not affect testis function, nagging concerns remained that a delayed onset of testicular effect might exist. The objectives of this study were to assess the effects of relatively longer treatment duration of triptolide on fertility, spermatogenesis, and epididymal sperm pathophysiology; and to evaluate the reversibility of these effects after the cessation of treatment. Adult male Sprague-Dawley rats were fed daily with either 30% gum acacia as a vehicle control (n = 12) or 100 microg/kg body weight (BW) of triptolide for 82 days (n = 12) followed by a recovery period of up to 14 weeks (n = 6). At the end of the treatment period, all rats treated with triptolide were sterile. Cauda epididymal sperm content decreased by 84.8% and sperm motility was reduced to zero. In addition, virtually all cauda epididymal sperm in the triptolide-treated group exhibited severe structural abnormalities. The most striking changes observed were head-tail separation, premature chromatin decondensation of sperm nuclei, a complete absence of the plasma membrane of the entire middle and principle pieces, disorganization of the mitochondrial sheath, and aggregation of many sperm tails. Longer treatment duration of triptolide also affected spermatogenesis, with marked variability in the response of individual animals. The degree of damage ranged from apparently normal-looking seminiferous tubules to flattened seminiferous epithelium lined by a single layer of cells consisting of Sertoli cells and a few spermatogonia. Affected tubules exhibited intraepithelial vacuoles of varying sizes, multinucleated giant cells, germ cell exfoliation, and tubular atrophy. Recovery occurred as early as 6 weeks after cessation of treatment. By 14 weeks, 4 out of 6 triptolide-treated males were fertile and the females that were impregnated by 3 out of 4 triptolide-treated male rats produced apparently normal litters. These results suggest that triptolide has 2 phenotypic effects on mature and maturing germ cells. The first action appears earlier and manifests mainly in epididymal sperm. The second action presumably is directly on germ cells in testis and causes a variable impairment of spermatogenesis that may not be completely reversible. It is unclear if the earlier effect is a delayed manifestation of subtle testicular injury or post-testicular action.     

Activation of the peripheral endocannabinoid system in human obesity

Obesity is the main risk factor for the development of type 2 diabetes. Activation of the central endocannabinoid system increases food intake and promotes weight gain. Blockade of the cannabinoid type 1 (CB-1) receptor reduces body weight in animals by central and peripheral actions; the role of the peripheral endocannabinoid system in human obesity is now being extensively investigated. We measured circulating endocannabinoid concentrations and studied the expression of CB-1 and the main degrading enzyme, fatty acid amide hydrolase (FAAH), in adipose tissue of lean (n = 20) and obese (n = 20) women and after a 5% weight loss in a second group of women (n = 17). Circulating levels of anandamide and 1/2-arachidonoylglycerol were increased by 35 and 52% in obese compared with lean women (P < 0.05). Adipose tissue mRNA levels were reduced by -34% for CB-1 and -59% for FAAH in obese subjects (P < 0.05). A strong negative correlation was found between FAAH expression in adipose tissue and circulating endocannabinoids. Circulating endocannabinoids and CB-1 or FAAH expression were not affected by 5% weight loss. The expression of CB-1 and FAAH was increased in mature human adipocytes compared with in preadipocytes and was found in several human tissues. Our findings support the presence of a peripheral endocannabinoid system that is upregulated in human obesity.     

内源性大麻素系统调节瘙痒的研究进展

背景 很多药物和疾病都能引起瘙痒,但目前有关瘙痒的病理生理学还不完全清楚.研究发现,内源性大麻素系统在调节瘙痒中起着重要的作用,影响着瘙痒的发生与发展.目的 就近年来国内外有关内源性大麻素系统调节瘙痒的文献作一综述. 内容 大麻素受体1 (cannabinoid receptor 1,CB1)激动剂缓解瘙痒,拮抗剂诱发瘙痒.大麻素受体2(cannabinoid receptor 2,CB2)拮抗剂、内源性大麻素类化合物和脂肪酰胺水解酶(fatty acid amide hydrolase,FAAH)间接抑制瘙痒.此外,内源性大麻素的止痒作用可能部分是通过瞬时受体电位香草类受体(transient receptor potential vanilloid type,TRPV)介导的.趋向 内源性大麻素系统可能成为将来各种病因学全身性瘙痒的止痒靶点,但其调节瘙痒的机制还不十分清楚,需要进一步的研究和探讨.     

Role in anxiety behavior of the endocannabinoid system in the prefrontal cortex

In the present study we explored with a multidisciplinary approach, the role of anandamide (AEA) in the modulation of anxiety behavior at the level of the prefrontal cortex (PFC). Low doses of the metabolically stable AEA analog, methanandamide, microinjected into the PFC, produced an anxiolytic-like response in rats, whereas higher doses induced anxiety-like behaviors. Pretreatment with the selective antagonist of CB1 or TRPV1 receptors (AM251 and capsazepine, respectively) suggested that the anxiolytic effect evoked by AEA might be due to the interaction with the CB1 cannabinoid receptor, whereas vanilloid receptors seem to be involved in AEA anxiogenic action. When AEA contents in the PFC were increased by microinjecting the selective inhibitor of fatty acid amide hydrolase (FAAH), URB597, we observed an anxiolytic response only at low doses of the compound and no effect or even an anxiogenic profile at higher doses. In line with this, a marked decrease of AEA levels in the PFC, achieved by lentivirus-mediated local overexpression of FAAH, produced an anxiogenic response. These findings support an anxiolytic role for physiological increases in AEA in the PFC, whereas more marked increases or decreases of this endocannabinoid might lead to an anxiogenic response due to TRPV1 stimulation or the lack of CB1 activation, respectively.     

Laser irradiation affects enzymatic antioxidant system of streptozotocin-induced diabetic rats

The aim of the present study was to analyze the effect of low-power laser irradiation in the antioxidant enzymatic system of submandibular (SMG) and parotid (PG) salivary glands of streptozotocin-induced diabetic rats. The animals were randomly divided into six groups: three diabetic groups (D0, D5, and D20) and three non-diabetic groups (C0, C5, and C20), according to laser dose received (0, 5, and 20 J/cm², respectively). Areas of approximately 1 cm² were demarcated in the salivary glands (each parotid and both submandibular glands) and after irradiated according to Simões et.al. (Lasers Med Sci 24:202–208, 2009). A diode laser (660 nm/100 mW) was used, with laser beam spot of 0.0177 cm2. The group treated with 5 J/cm² laser dose was subjected to irradiation for 1 min and 4 s (total irradiation time) and the group treated with 20 J/cm² laser dose was subjected to irradiation for 4 min and 16 s. Twenty-four hours after irradiation the animals were euthanized and the salivary glands were removed for biochemical analysis. The total antioxidant values (TA), the activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase enzymes were determined. SOD and CAT activities, as well as TA were higher in SMG of irradiated diabetic rats. However, in SMG of non-diabetic rats, laser irradiation decreased TA values and led to an increase in the CAT activity. In addition, there was a decrease in the activity of CAT in PG of diabetic and non-diabetic animals after laser irradiation. According to the results of the present study, low-power laser irradiation can affect the enzymatic antioxidant system of salivary glands of streptozotocin-induced diabetic rats.     

Quantitative maintenance of spermatogenesis in cyclosporine-treated rats by exogenous administration of testosterone propionate

The authors had previously shown that the subcutaneous administration of cyclosporine (CsA) resulted in an impairment of spermatogenesis. Testosterone levels declined and gonadotropin levels increased, suggesting that CsA primarily affects the synthesis and secretion of testosterone. In this study, the authors attempted to determine whether the exogenous administration of testosterone would maintain spermatogenesis in animals treated with a very high dose of CsA. Sexually mature, male Sprague-Dawley rats were treated subcutaneously with CsA (40 mg/kg per day) alone, or in combination with testosterone propionate (TP; 2 and 5 mg/d per rat), for 14 days. As expected, CsA reduced the body and reproductive organ weights and the levels of serum testosterone, while elevating the levels of follicles-stimulating hormone (FSH) and luteinizing hormone (LH). Quantitative analysis of spermatogenesis revealed a decline in all the different types of germ cells in tubules at stage VII of the cycle of the seminiferous epithelium. Administration of TP in 2 and 5 mg/d per rat doses restored the body and reproductive organ weights and the circulating levels of FSH. The serum levels of LH were below the assay's minimum level of detectability. Analysis of spermatogenesis revealed a dose-dependent increase in the germ cell counts after the administration of 2 and 5 mg of TP. The circulating levels of CsA were also significantly reduced after TP administration. These results revealed that CsA-induced alteration in spermatogenesis can be prevented by the exogenous administration of testosterone.     

Prolonged suppression of spermatogenesis by oestrogen does not preserve the seminiferous epithelium in procarbazine-treated rats

We examined the hypothesis that induction of reversible testicular atrophy, subsequent to withdrawal of gonadotrophin support, would alleviate the testicular toxicity of the anti-cancer drug procarbazine. In rats, severe but reversible testicular atrophy and suppression of spermatogenesis were induced 56 days after the subcutaneous insertion of a silastic implant containing oestradiol-17 beta. The effect of this treatment upon the testicular toxicity of four weekly doses of procarbazine (200 mg kg-1) was examined 56 days after the termination of procarbazine/oestrogen treatment. At this time the testicular endocrine and spermatogenic functions were close to normal in rats which has received only oestradiol-17 beta. Procarbazine produced severe testicular atrophy which was associated with azoospermia and destruction of the germinal epithelium. Serum LH and FSH concentrations were raised and were associated with low serum concentrations of both testosterone and androgen-binding protein. The combination of procarbazine with the oestrogen treatment did not change any of the testicular toxicity and in some cases it appeared to be exacerbated. In contrast to these experiments other studies have indicated that the testis can be protected if spermatogenesis is reversibly suppressed by other agents which are also active via the pituitary endocrine system. The data would therefore suggest that protection is achieved either by some testicular change other than withdrawal of pituitary gonadotrophin support or that oestradiol-17 beta has additional activity which is permissive for the development of the testicular toxicity of procarbazine.     

Role of cannabinoids and the endocannabinoid system in modulation of diabetic cardiomyopathy

Diabetic complications, chiefly seen in long-term situations, are persistently deleterious to a large extent, requiring multi-factorial risk reduction strategies beyond glycemic control. Diabetic cardiomyopathy is one of the most common deleterious diabetic complications, being the leading cause of mortality among diabetic patients. The mechanisms of diabetic cardiomyopathy are multi-factorial, involving increased oxidative stress, accumulation of advanced glycation end products (AGEs), activation of various pro-inflammatory and cell death signaling pathways, and changes in the composition of extracellular matrix with enhanced cardiac fibrosis. The novel lipid signaling system, the endocannabinoid system, has been implicated in the pathogenesis of diabetes and its complications through its two main receptors: Cannabinoid receptor type 1 and cannabinoid receptor type 2, alongside other components. However, the role of the endocannabinoid system in diabetic cardiomyopathy has not been fully investigated. This review aims to elucidate the possible mechanisms through which cannabinoids and the endocannabinoid system could interact with the pathogenesis and the development of diabetic cardiomyopathy. These mechanisms include oxidative/ nitrative stress, inflammation, accumulation of AGEs, cardiac remodeling, and autophagy. A better understanding of the role of cannabinoids and the endocannabinoid system in diabetic cardiomyopathy may provide novel strategies to manipulate such a serious diabetic complication.     

Effects of the chronic use of dehydroepiandrosterone (DHEA) on testicular weight and spermatogenesis: Experimental study in rats

Aim: The complete biological effects of chronicuse of dehydroepiandrosterone (DHEA), reportedas a weak androgen, are not completelyunderstood. The aim of the present study is toevaluate the effects of chronic administrationof DHEA on the spermatogenesis in rats.Methods: Male Wistar rats, 4 months old, wereselected for the study. The animals weredivided into two groups. Group 1 (n = 9) receivedplacebo (saline solution) 0.5 ml/day and Group2 (n = 15) received DHEA 5 mg/kg/day. Both thegroups received the respective treatments 5days a week during 10 months. At the end of theexposure, the rats were sacrificed and thetestes removed, weighed and processed forhistologic analysis. Spermatogenesis wasevaluated as the mean number of seminiferoustubules with and without spermatids inmaturation phase in their lumen, in fiverandom fields on the same slide.Results: The median levels of serum totaltestosterone and dehydroepiandrosterone sulfatewas measured in the two groups. Significanthigher concentrations in total testosterone(2.06 ± 0.4 vs. 0.80 ± 0.2; p < 0.05) andDHEAS (222.1 ± 41.5 vs. 2.0 ± 0.3) wereobserved in the group treated with DHEA ascompared to the control group. The mean weightsof the right testes were 1.59 ± 0.3 ingroup 1 and 1.58 ± 0.2 g in group 2(p > 0.05). These values for the left testeswere 1.57 ± 0.3 and 1.55 ± 0.3 g,respectively (p > 0.05). The histologicanalysis showed a mean of 13.5 ± 1.5 and12.8 ± 1.8 seminiferous tubules per field inthe groups 1 and 2, respectively (p > 0.05).The same analysis demonstrated that in thecontrol group 0.06 ± 0.1 of the tubulespresented without spermatids in maturationphase and in the DHEA group this was observedin 0.22 ± 1.2 of the tubules (p < 0.05).Conclusion: Chronic administration of DHEA inthe present dose did not show any detectableeffect on the quantitative and qualitativeanalyses of spermatogenesis in rats.     

Distribution and function of the endocannabinoid system in the rat and human bladder

Introduction and hypothesis

Our aim was to compare expression and distribution of cannabinoid receptors CB1 and CB2, transient receptor potential vanilloid receptor 1 (TRPV1), and modulating enzymes in human and rat bladder. We also evaluated effects of cannabinoid agonists (ACEA, agonist of CB1; GP1A, agonist of CB2) on contractile responses of rat bladder strips.

Methods

Distribution and expression of CB1, CB2 and TRPV1 receptors and enzymes fatty acid amide hydrolase (FAAH) and N-acyl phosphatidylethanolamine-hydrolyzing phospholipase D (NAPE-PLD) was studied using immunohistochemistry and immunoblotting on human and Wistar rat bladders. The effects of cannabinoid agonists on contractile responses of isolated rat bladder strips to electrical-field stimulation (EFS) or carbachol-evoked responses were determined.

Results

Immunoreactivity for CB1 and TRPV1 receptors and FAAH and NAPE-PLD was present in the bladder of both species. CB1 proteins were of different sizes in rat (57 kDa) and human (40 kDa) bladder. CB2 (45 kDa in both species) immunolocalised to both urothelium and detrusor muscle in human bladder but only to detrusor muscle in rat. FAAH proteins were found at 55 kDa for both species. Rat NAPE-PLD protein (44 kDa) was similar in size to that in human bladder (45 kDa). TRPV1 proteins were found at 104 kDa in both species. ACEA (10^?4?M) attenuated bladder contractions by 35?±?5.4 % (p?<?0.001); GP1a had no effect despite the EC₅₀ values for the carbachol dose–response curves for both agonists being significantly shifted to the right.

Conclusions

The endocannabinoid system is functionally expressed in both species, with CB1 receptors showing both pre- and postsynaptic inhibitory effects on rat bladder contraction, whereas CB2 acts only postsynaptically.     

Long-term effect of vasectomy on spermatogenesis in men: a morphometric study

Spermatogenic damage may occur after vasectomy, and the damage is pressure mediated, occurring when the occluded reproductive tract is unable to accommodate additional sperm produced by the testis. This study aimed to determine the long-term effect of vasectomy on spermatogenesis in humans and clarify how the balance between sperm production in the testis and sperm storage in or removal from the tract might be maintained. During inguinal hernia repair, an open biopsy was performed to obtain testicular tissue blocks from 51 Chinese men (aged ≥50 years), of whom 25 (control group) had not undergone vasectomy and 26 (vasectomized group) had undergone bilateral vasectomy 22–42 years before. Methacrylate resin-embedded testicular sections were made, and morphometric studies were performed using light microscopy. In addition, sizes of the testis and epididymis were estimated with ultrasonography. The testicular tissue blocks obtained from one control and seven vasectomized men consisted almost completely of connective tissue. In the other 43 men, significant differences were not found between the two groups in the testicular or epididymal size, qualitative histology or quantitative parameters including the mean diameter or volume fraction of the seminiferous tubules. In conclusion, sperm production and sperm storage/removal reached a static equilibrium after vasectomy, likely due to spermatogenic degeneration or less sperm production as a result of aging or due to vasectomy-induced testicular (interstitial) fibrosis. Thus, complications that might occur in association with overproduction of sperm and distension of the tract would disappear or be relieved with time.     

Effect of nicotine on spermatogenesis in adult albino rats

This study aimed to assess the effects of nicotine on spermatogenesis in 140 mature male albino rats divided into group A (controls), group B (sham controls), group C (nicotine treated) and group D (nicotine withdrawal). Group C was subdivided into CI, CII, CIII according to the dose of injected nicotine (0.2, 0.4 and 0.6 mg nicotine per 100 g per day), where each subgroup was further subdivided according to the treatment duration into subgroups a, b and c that received nicotine for 2, 4 and 8 weeks. Group D received nicotine for 8 weeks followed by withdrawal for another 8 weeks to assess testicular recovery. Testicular tissue sections were subjected to haematoxylin and eosin, Masson's trichrome stains and morphometry. The results showed that nicotine caused degenerative changes in the seminiferous tubules, revealed by altered general tubular architecture, decreased thickness of the spermatogenic cell masses, Sertoli cell vacuolation and thickened basal lamina. These changes were proportional to the nicotine dose and duration. Following nicotine withdrawal, regeneration of the damaged seminiferous tubules was observed to be rather complete in CI group. It is concluded that nicotine could adversely affect testicular spermatogenesis in a dose- and time-dependent manner which would be almost reversible after nicotine withdrawal, especially after small doses.