Age-dependent differences in the effects of 1, 2-dibromo-3-chloropropane (DBCP) on fertility, sperm count, testicular histology and hormonal profile in rats

This study was set up to determine if there are any age-dependent differences in the adverse effects of DBCP on the reproductive system of male rats. Groups of male rats were injected at the ages of 7,30 or 90 days with a single (50 mg kg-1 body weight) or repeated (20 mg kg-1 body weight once a week for 3 weeks) dose of DBCP, dissolved in DMSO. Ninety days after the last injection the males' fertility was estimated and the animals were killed. Blood was collected for future hormone assays, organs were weighed, testes were then taken for histological studies and sperm counts. The results were compared with those of control peers. The results showed that animals injected at the ages of 7 or 90 days under both regimens of treatment were adversely affected. The damage was noted in their fertility rate, sperm production, testicular histology and hormonal profile. Those injected at the age of 30 days showed only an insignificant variation compared with controls.     

Testicular Damage Development in Rats Injected with Dibromochloropropane (DBCP)/Entwicklung eines Hodenschadens bei der Ratte durch Dibromchlorpropan

Dibromochloropropane (DBCP) is an effective nematocide which was shown to suppress spermatogenesis and cause infertility in men and rats exposed to the compound. These damages were described only after 6-8 weeks post injection. The present study was set to detect the early development of the testicular damages. Rats were injected s.c. with DBCP 50 mg/kg. Control animals were injected with the vehicle alone (DMSO). Groups of animals were sacrificed 24 h, 1, 2, 3 and 4 weeks post injection. Body weight of DBCP treated animals was reduced from the second week post injection. Organs' weights of the DBCP treated rats, corrected for differences in body weights, were similar to those of controls. Four weeks post injection testes and accessory gland weights were significantly reduced as compared with controls. Percentage of damaged tubules in the DBCP treated animals were elevated from 16.6 +/- 3.5 at the first day to 70.2 +/- 6.4 at the 4th weeks. Concomitantly with the advance of tubular damage was a reduction in epididymal sperm count in the DBCP treated rats. One week post injection histological changes were evident. These included multinucleated giant cells and tubules blocked with sperm granuloma. It seems that alterations of spermatogenesis appear earlyer and are already noticeable one week post injection.     

Long Term Effects of Dibromochloropropane (DBCP) on Male Rats'' Reproductive System

Adult male rats were injected s.c. once a week for 3 weeks with DBCP, 20 mg/kg B.W. Animals were sacrificed 5, 9, 13, 17, 25 and 50 weeks after last injection. Body weight was recorded once a week. Prior to sacrifice each male was presented with proestral females in order to determine the male's mating behaviour and fertility. Testes were removed, weighed and taken for standard histological examination. DBCP treatment caused a reduction of body weight which reverted back to control levels some 17 weeks post injection. Testes weights were reduced and remained low despite the recovery of body weight. Generally, all males showed normal mating behaviour but most of them were infertile. Testicular histology showed a correlation between decreasing testicular weight and increasing percentage of degenerated seminiferous tubules, which was on the other hand correlated with decreasing tubular diameter. Serum levels of FSH and LH were significantly increased in the infertile DBCP treated males while values for the fertile ones were similar to those of controls. There were no differences in serum testosterone levels between DBCP treated and control animals. It is concluded that in DBCP treated rats testicular degenerative damages are associated with increased circulating gonadotrophin levels and with normal testosterone levels. Although mating behaviour is unaffected fertility is depressed and does not recover for at least 50 weeks post injection. It is suggested that DBCP treatment affects mainly the activity of the Sertoli cells while the Leydig cells are affected to a much lesser degree.     

The Effect of Dibromochloropropane (DBCP) on In Vitro Cyclic AMP Levels and Testosterone Production in Rat Testes

Adult male rats were injected s.c. once a week for 3 weeks with DBCP, 20 mg/kg BW. Animals were sacrified 20 weeks after last injection. Body and testes weights were recorded and testes were taken for standard histological preparation and for in vitro experiments. The in vitro experiments were carried out on testes slices (90-110 mg) incubated for 3 h with or without the addition of hCG to the incubation medium. Cyclic AMP content of the tissue as well as testosterone released into the incubation medium were determined. Testes weights of DBCP treated animals were 68% lower than that of controls. All semiferous tubules were damaged and shrunken, thus, their number per microscope field was 2.6 times that of controls. Cyclic AMP levels in testes slices were similar in both DBCP treated and controls. The addition of hCG stimulated cyclic AMP accumulation to a much higher level in the DBCP treated than in controls. When calculated per one pair of testes the content in unstimulated pair was more than twice that of DBCP treated. Stimulation of hCG increased both DBCP treated and controls to similar levels. Testosterone release into the medium by slices was higher in DBCP treated than in controls and so was also the increment due to hCG stimulation. Similar results were obtained when testosterone release was calculated per one pair of testes. It is suggested that since the major testicular compartment damaged by DBCP is the tubular one, the proportion of the interstitium per testicular unit weight is larger than in controls, thus, cyclic AMP content increment due to hCG stimulation is much higher.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of p-nonylphenol on the fertility potential of male rats after gestational, lactational and direct exposure

There is growing concern that abnormalities in male reproductive health are becoming more frequent. The most fundamental change has been the striking decline in sperm counts and semen quality. The effect of maternal exposure of rats to the oestrogenic environmental substance p-nonylphenol (p-NP) was determined in this study. Exposure to p-NP for the experimental period impaired general growth. The lower testicular mass indicated a direct toxic effect on the testis in animals exposed to p-NP during foetal life, the postnatal period and after weaning until termination at 10 weeks of age. The epididymal mass was also negatively affected by p-NP; this was supported by the decrease in the epididymal ratio. The total cauda epididymal sperm count was significantly lower in the 250 mg kg-1 p-NP dosage group compared to the control and 100 mg kg-1 p-NP groups. The overall lower sperm count with increased p-NP concentrations corresponded with the decreased testicular and epididymal masses. This emphasized the toxicity of p-NP on both testis and epididymis. Seminiferous tubule diameter, lumen diameter and seminiferous epithelium thickness were smaller in the exposed groups, even at the low dose level. These histological measurements further supported the finding of a low testicular mass. In spite of the measurements being smaller, p-NP had no effect on the stages of spermatogenesis except for one animal with disrupted spermatogenesis in some tubules, while others were normal.     

Antispermatogenic activity of Morinda lucida extract in male rats

Aim： To investigate the effect of Morinda lucida Benth （Rubiaceae） on the reproductive activity of male albino rats. Methods： Two groups of rats were treated with 400 mg/（kg.d） of Morinda lucida leaf extract for 4 and 13 weeks, respectively. The control rats received the vehicle. All the treated rats had corresponding recovery groups. At the end of each experimental period, animals were killed and organ weights, sperm characteristics, serum testosterone levels, histology of the testes and fertility were assessed. Results： Morinda lucida leaf extract did not cause any changes in body and somatic organ weights, but significantly increased the testis weight （P 〈 0.05）. The sperm motility and viability, and the epididymal sperm counts of rats treated for 13 weeks were significantly reduced （P 〈 0.05）. Sperm morphological abnormalities and serum testosterone levels were significantly increased （P 〈 0.05）. There were various degrees of damage to the seminiferous tubules. The extract reduced the fertility of the treated rats by reducing the litter size. Reversal of these changes, however, occurred after a period of time. Conclusion： The extract of Morinda lucida has reversible antispermatogenic properties.     

Ameliorative effect of nerolidol on cyclophosphamide-induced gonadal toxicity in Swiss Albino mice: Biochemical-, histological- and immunohistochemical-based evidences

Cyclophosphamide (CP) is commonly used as antineoplastic and immunosuppressant drug with noticeable gonadotoxic profile. Nerolidol (NER) is a sesquiterpene with potent antioxidant and anti-inflammatory properties. Thus, the present study was designed to explore its possible gonadal protective potential against cyclophosphamide-induced testicular, epididymal, seminal and spermatozoal toxicities. Animals were divided into five groups: control (normal saline for 14 days), treatment group (NER 200 and 400 mg/kg, p.o) for 14 days along with a single dose of cyclophosphamide (200 mg/kg, i.p) on 7^th day, toxic and Per se groups (cyclophosphamide 200 mg/kg i.p) on 7^th day and NER 400 mg/kg for 14 days respectively. Animals were sacrificed on the 15 day, and body weight, weight of reproductive organs, testosterone level, sperm count, biochemical parameters, histopathological and immunohistochemical studies were performed in the testes, epididymis and in the serum. CP administration induced oxidative stress, nitrative stress, inflammation, reduced testosterone level, sperm count, increased expression of MPO and caused histological aberrations in the testes, epididymis and seminal vesicles. CP caused reduced sperm count, sperm motility and testosterone level which got reversed upon treatment with nerolidol in a dose-dependent manner. Nerolidol thus acted as a gonadoprotective molecule and prevented the gonadotoxicity of CP.     

Effects of cyclosporin A on male reproduction in rats

Effects of cyclosporin (Cs) on male reproduction in rats were examined. A dose-dependent decrease of the sperm counts in the cauda epididymis was observed 6 weeks after Cs was administered. A significant decrease of sperm motility was also observed in the each Cs-treated group in any observational period after Cs injection, which suggested an injury to epididymis by Cs. A slight damage of the seminiferous tubules was demonstrated 6 weeks after administration of 40 or 60 mg/kg of Cs. No change in serum levels of luteinizing hormone and testosterone was demonstrated throughout the experiment. But serum levels of follicle-stimulating hormone were significant high in any observational period except 6 weeks after Cs injection. It was concluded that Cs gave injuries to both spermatogonia and epididymal function in rat.     

氰戊菊酯对大鼠精子及生殖激素的影响

目的探讨氰戊菊酯(Fen)对雄性大鼠精子计数、活力以及生殖激素的影响。方法成年雄性SD大鼠,分别以0、20、40、80mg/kg剂量的Fen连续灌胃染毒15和30d,按常规方法进行精子计数和精子活力检测,应用放射免疫法和化学发光免疫法测定大鼠血清卵泡刺激素(FSH)、黄体生成素(LH)、睾酮(T)、雌二醇(E2)和睾丸匀浆中T、E2水平。结果Fen染毒15d时,与0mg/kg组相比,40mg/kg剂量组精子数量明显减少(P<0.01),20和40mg/kg组睾丸匀浆中T水平显著降低(P<0.01,P<0.05),血清LH、FSH水平随染毒剂量的增加而升高,且FSH水平和染毒剂量有显著的剂量-效应关系(P<0.05);Fen染毒至30d时,各组间精子数量差异不显著,与0mg/kg组相比,40mg/kg剂量组(a+b)级精子活力显著降低(P<0.05),血清LH、FSH水平随染毒剂量的增加而升高,但差异不显著。结论Fen对雄性大鼠有明显的生殖毒性作用,能够改变血清和睾丸中的生殖激素水平。     

Induction of chemical castration in male rats by a new long-acting LHRH-antagonist

LHRH-antagonists might represent a useful new type of androgen deprivation to treat prostatic cancer. In this context adult intact male rats were treated subcutaneously with different concentrations of the new LHRH-antagonist antide either once (1, 3, 6, 10, 15 mg/kg) or on 5 consecutive days (5 x 3 mg/kg). The effect on serum concentration of LH and testosterone and the effect on the weights of testes, prostate, and seminal vesicles was investigated after different periods of time (24 hours, 1, 2, 3, 5, and 8 weeks). Histological evaluation of the testes was also performed. A clear dose-dependent inhibitory effect on the above-mentioned parameters was observed. The most effective treatment schedule was the single application of 15 mg/kg resulting in castration-like inhibition of prostate weights and marked inhibition of spermatogenesis within 2 weeks, which was maintained 8 weeks after the injection. Serum LH and serum testosterone concentrations were below the detection limit of the assay within 2 weeks and showed first signs of recovery after 8 weeks. Histologically, no signs indicative of irreversible effects (testes) were observed. To summarize, the LHRH-antagonist antide was found to have a profound long-lasting inhibitory but reversible effect on the reproductive system of adult intact male rats. These data emphasize the suitability of this type of compound for the treatment of prostatic cancer.     

Relationship between dyslipidaemia and semen quality and serum sex hormone levels: an infertility study of 167 Japanese patients

A prospective study was performed in the Reproduction Center of Ichikawa General Hospital (Chiba, Japan) to assess the relationship between dyslipidaemia and sperm quality and serum hormone levels in male patients in Japan. The semen parameters and blood samples were assessed in relation to several variables, including body mass index (BMI) and serum triglyceride (TG) levels. Between 2011 and 2012, 167 male partners of infertile couples aged 22–46 years (mean: 36.5 years) were referred to the reproduction centre. In total, 66 patients (39.5%) had hypertriglyceridaemia (TG level ≥ 150 mg dl^?1). There was no significant relationship between serum TG levels and sperm concentration or motility; however, the serum TG level was positively associated with the sperm morphological traits. Furthermore, the serum levels of glutamic oxaloacetic transaminase and glutamic pyruvic transaminase were associated with the serum TG levels. By contrast, a negative relationship between serum testosterone and TG levels was discovered.     

Accumulation of mercury and its effects on testicular functions in rats intoxicated orally by methylmercury

All forms of mercury are considered poisonous. Methylmercury, one organic form, is highly toxic to many organs. The aim of the present study was to assess the effects of this form on the reproductive system in the rat. For this, 20 male rats were divided into two groups. One, which is considered as reference, received tap water. The second group received tap water containing methylmercury at the rate of 20 mg l^?1 for 8 weeks. At the end of the experiment, blood samples were collected for the determination of total mercury and plasma testosterone. The left testes were used for the determination of total mercury and histological examination. Appropriate centrifugation was applied on right testes to extract interstitial and seminiferous tubular fluids. The epididymides were homogenised for the sperm count. Our results showed a dramatic fall in the plasma testosterone in the contaminated animals. The fall in plasmatic testosterone seems to be in relation with the decrease in the secretion of testosterone. In association with this, the concentration of testosterone in seminiferous tubules fluid dropped about 55% in the poisoned animals in comparison with the controls. Despite this, no decrease in the epididymal sperm count in contaminated rats was observed.     

Effect of Alstonia scholaris bark extract on testicular function of Wistar rats

Abstract Aim: To evaluate the antifertility effect ofAlstonia scholaris bark extract in male rats. Methods: In male Wistar rats Alstonia scholaris bark extract was given by oral route at a dose of 200 mg/day for 60 days. The fertility and testicular function were assessed by mating tests, sperm motility, sperm concentration, biochemical indices and testicular cell population dynamics. Results: Oral feeding with the extract at a dose of 200 mg/day for the period of 60 days did not cause body weight loss, while the weights of testes, epididymides, seminal vesicle and ventral prostate were significantly reduced. The production of step-19 spermatids was reduced by 79.6% in treated rats. The population of preleptotene and pachytene spermatocytes were decreased by 61.9% and 60.1%, respectively. Spermatogonia and Sertoli cell population were also affected. The seminiferous tubule and Leydig cell nuclear area were reduced significantly (P<0.01) when compared to the controls. Reduced sperm count and motility res     

精氨酸锌作为一种化学绝育剂的研究

本研究采用精氨酸锌及生理盐水,分别经80只正常性成熟Winstar大鼠的附睾尾注射0.1m1,观察48小时、1周、2周,3周及4周以后火鼠睾丸、附睾、输精管、前列腺的病变,结果显示经上述两种物质注射1周以后,睾丸均出现生精功能低下,间质细胞无异常,其精氨酸锌注射两周后,附睾尾管腔内即达到完全无精子,而生理盐水注射后仅导致附睾尾精子数量及活力大大降低,但始终不能达到完全无精子。此结果提示:精氨酸锌附睾尾注射可能成为一种新的男性绝育方法,值得进一步研究。     

Rose oil inhalation protects against formaldehyde-induced testicular damage in rats

In this experimental study, harmful effects of formaldehyde (FA) inhalation on sperm concentration, sperm quality, serum testosterone levels and the rat testes were investigated. In addition, the possible protective effects of rose oil against to these harmful effects were evaluated. For this purpose, 21 albino-Wistar rats were used. The rats in Group I were used as control group. When the rats of Group II were exposed FA (10 ppm/1 h) for 35 days, the rats of Group III inhalated rose oil (1 ml/1 h) after FA. The epididymal tissues were taken for sperm analysing and the testes were removed for histological examination. In addition, testosterone levels were determined from the blood samples. Although the testosterone levels, the epididymal sperm concentration, and the progressive sperm motility significantly decreased, the abnormal sperm rate significantly increased in the Group II when compared to Group I. In the Group III, these damages were seen less. When the rats in the Group II compared with the control group, there were serious histological damages. In the Group III, it was determined that the histological changes were less than group II. It can be expressed that serious damages occurred via formaldehyde exposure in male reproductive system and that the rose oil had protective effects against these damages.     

Effect of Sarcostemma acidum stem extract on spermatogenesis in male albino rats

AIM: To evaluate the possible antifertility activity of Sarcostemma acidum (Roxb) Voigt. stem extract in male rats. METHOD: Male rats were given 70% methanol extract of S. acidum stem orally at dose levels of 50 and 100 mg/kg/day for 60 days. Fertility was evaluated with mating test. Sperm motility and sperm density in cauda epididymides were also assessed. Biochemical and histological analyses were performed on blood samples and on the reproductive organs. RESULTS: S. acidum stem extract resulted in an arrest of spermatogenesis without any systemic side effect. Sperm motility as well as sperm density was reduced significantly. Treatment caused a 80% reduction in fertility at the 50 mg dose and complete suppression of fertility at the 100 mg dose. There was no significant change in RBC and WBC count, hemoglobin, haematocrit, sugar and urea in the whole blood and cholesterol, protein and phospholipid in the serum. The protein and glycogen content of the testes, fructose in the seminal vesicle and protein in epididymides were significantly decreased. Cholesterol in the testes was elevated. Treatment at both of the doses caused a marked reduction in the number of primary spermatocytes (preleptotene and pachytene), secondary spermatocytes and spermatids. The number of mature Leydig cells was decreased, and degenerating Leydig cells was increased proportionately. CONCLUSION: S. acidum stem extract arrests spermatogenesis in male rats without noticable side effects.     

口服丙烯酰胺对雄性大鼠生长发育及生殖机能的影响

目的:研究丙烯酰胺对雄性大鼠的生殖毒性作用。方法:30只21日龄断奶未成熟雄性大鼠随机分为3组,实验组Ⅰ和实验组Ⅱ分别通过自由饮水方式口服5 mg/kg.d和10 mg/kg.d的丙烯酰胺溶液8周,对照组饮用自来水。分两批(第4周和第8周时)对体重、脏器重等指标进行检测,并做睾丸和附睾的组织形态学观察;第8周时,同时检查附睾尾精子密度和精子形态。结果:两实验组大鼠体重增加显著低于对照组(P<0.05),至实验8周时,睾丸、附睾性器官发育已受到影响,实验组Ⅱ大鼠附睾尾部精子密度明显低于对照组(P<0.05),实验组Ⅰ与对照组差异不显著(P>0.05)。睾丸出现不同程度的病理变化,发生调亡的生精小管周围间质细胞显著增多(P<0.05)。结论:丙烯酰胺会对生精小管产生毒性作用而导致雄性大鼠精子生成减少。     

3,3 diindolylmethane leads to apoptosis,decreases sperm quality,affects blood estradiol 17 β and testosterone,oestrogen (α and β) and androgen receptor levels in the reproductive system in male rats

3,3 Diindolylmethane (DIM) is a major digestive product of indole‐3 carbinol, obtained from Brassica family vegetables such as broccoli, cabbage and Brussels sprouts. This study aimed to investigate the effects of DIM on sperm parameters, histological structures of testicular tissues, blood testosterone (T) and estradiol 17‐β (E2) in male rats. Thirty‐eight male Sprague Dawley rats were used. Rats were divided into four groups: Group I: referred as Control group, received corn oil only; Group II: as DIM‐10, rats received 10 mg kg^?1 DIM; Group III: as DIM‐50, rats received 50 mg kg^?1 DIM; Group IV: as DIM‐100, received 100 mg kg^?1 DIM during 53 days. Spermatological parameters, malondialdehyde (MDA) levels of testes and serum T and E2 levels were assayed. Histopathological examinations of tests were done. DIM caused an increase in MDA levels. It decreased motility and live sperm rates and increased degeneration of testicular tissues. While DIM‐10 did not affect abnormal sperm rate, higher concentrations increased the abnormalities. Sperm density was higher in DIM‐10 groups when compared to both other groups. Only DIM‐50 had an anti‐androgenic effect among all groups. Only, DIM‐10 showed anti‐estrogenic activity as compared to higher DIM groups. In conclusion, DIM (i) had side effect on some sperm characteristics, (ii) increased the MDA levels and (iii) led to histological degeneration of testicular tissues and apoptosis in a dose‐dependent manner.     

Long‐term ofloxacin testicular toxicity: an experimental study

The aim of this study was to assess the long‐term toxic effect of ofloxacin on the testes and epididymides of 72 adult male albino rats. The rats were divided into group A and group B. Group A, which received ofloxacin for 14 days, was subdivided into two subgroups; LD‐14 received low dose 72 mg KBW^?1 daily and HD‐14 received high dose 216 mg KBW^?1 daily. Group B, which received ofloxacin for 28 days, was subdivided into two subgroups; LD‐28 received 72 mg KBW^?1 and HD‐28 received 216 mg KBW^?1 daily. Two matched control groups were followed up for 14 and 28 days respectively. The animals were evaluated for body weight, testicular weight, relative testicular weight, serum testosterone (T), epididymal sperm analysis (sperm count, motility, morphology, curvilinear velocity, linear velocity and linearity index) and testicular histopathology. The adverse effects of ofloxacin were correlated with increased treatment duration and/or dose. It is concluded that long‐term ofloxacin has a direct detrimental effect on the testicles of albino rats at the studied doses and durations.     

The Anti-Reproductive Effects of Long Term Oral Administration of Cadmium on the Adult Male Rat

The toxic effects of prolonged oral administration of cadmium on gametogenic and endocrine function of testes of adult rats were investigated. The experimental animals received daily, for 3, 6, 12 or 15 months, pellets containing 8.8 mg or 88 mg of cadmium chloride per kg body weight.
The rats treated with the higher doses of cadmium for 12 and 15 months showed a marked reduction in absolute weight of testes accompanied by histological signs of impairment of seminiferous tubules. There were no necrotic changes but a number of cross-sections of seminiferous tubules were deprived of spermatocytes and spermatids, reaching about 50 per cent of the tubules in the rats treated with higher doses of cadmium. The appearance of histological changes in rats treated for 12 and 15 months correlated with cumulation step of cadmium in testes and with alterations in serum concentration of LH but not of testosterone. Therefore, we suppose that under these experimental conditions the impairment of seminiferous tubules was induced by the direct influence of cadmium on germinal epithelium beginning the moment when cadmium reaches an effectively toxic concentration in testis.