Microcystins cause embryonic toxicity in mice

Microcystins produced by freshwater cyanobacteria are potent hepatotoxins and can cause animal intoxications and human illnesses. In the present study, the effects of microcystins on the embryonic development of Kunming mice were determined using cell extracts of Microcystis aeruginosa from the Nanwan reservoir, China. Forty-eight pregnant mice were divided into four groups of 12 mice. Pregnant mice in three experimental groups were injected intraperitoneally with cell extracts at doses equivalent to 3, 6, or 12 μg microcystins/kg body weight daily from gestational days 6–15, while the mice in the control group were injected on the same schedule with sterilized saline. Mice were killed on the 18th day of gestation and embryonic and fetal developmental indexes checked. The fetal mice were also examined for anomalies of external, skeletal, and internal organs. The results demonstrated a significant decrease in body weight gain of pregnant mice in the 12 μg/kg dose group when compared to the control group (p<0.05). Differences in mean body weight, body length, and tail length of the fetuses were also found in these two groups (p<0.05). However, no significant difference in these characteristics was detected in the 6 or 3 μg/kg dose groups when compared to the control group (p>0.05). Four fetuses in the 6 μg/kg body dose group were found to have a curving tail. Additionally, petechial hemorrhage and hydropic degeneration were observed in the livers of fetuses in the 6 and 12 μg/kg experimental groups. These results suggested that microcystins had both maternal and embryonic toxicity in mice.     

Sub-acute intravenous administration of silver nanoparticles in male mice alters Leydig cell function and testosterone levels

The aim of this study was to determine whether short-term, in vivo exposure to silver nanoparticles (AgNPs) could be toxic to male reproduction. Low dose (1 mg/kg/dose) AgNPs were intravenously injected into male CD1 mice over 12 days. Treatment resulted in no changes in body and testis weights, sperm concentration and motility, fertility indices, or follicle-stimulating hormone and luteinizing hormone serum concentrations; however, serum and intratesticular testosterone concentrations were significantly increased 15 days after initial treatment. Histologic evaluation revealed significant changes in epithelium morphology, germ cell apoptosis, and Leydig cell size. Additionally, gene expression analysis revealed Cyp11a1 and Hsd3b1 mRNA significantly upregulated in treated animals. These data suggest that AgNPs do not impair spermatogonial stem cells in vivo since treatment did not result in significant decreases in testis weight and sperm concentrations. However, AgNPs appear to affect Leydig cell function, yielding increasing testicular and serum testosterone levels.     

Toxic effects of zearalenone and its derivatives alpha-zearalenol on male reproductive system in mice

The current study evaluated effects of zearalenone (ZEA) and its derivative alpha-zearalenol (alpha-ZOL) on male mouse semen quality, fertility and serum testosterone concentrations. Adult male mice were exposed to intraperitoneal (i.p.) injection of ZEA or alpha-ZOL at 0, 25, 50, and 75 mg/kg body weight (b.w.) daily for 7 days, and then mated with sexually mature untreated female mice. Semen quality, serum testosterone concentrations and fertility of treated mice were assessed. The results showed that the number of abnormal spermatozoa increased and the amount of live spermatozoa decreased significantly in males treated with ZEA at all doses. As well, a significant decrease in spermatozoa with integrated acrosome was observed in mice treated with 50 and 75 mg/kg b.w. alpha-ZOL. Significantly low pregnancy rate was observed when females were mated with ZEA or alpha-ZOL exposed males. Male mice exposed to ZEA had significant reductions in b.w. and relative epididymis weights. However, relative seminal vesicle weights were higher than those of controls. Conversely, significant increases in b.w. and relative preputial gland weight were observed in mice exposed to alpha-ZOL. Testicular and cauda epididymal sperm counts, efficiency of sperm production and serum testosterone concentrations were significantly reduced in mice treated with ZEA or alpha-ZOL at all doses in a dose-dependent manner. In conclusion, we demonstrate that ZEA or alpha-ZOL have adverse effects on reproductive system of adult male mice.     

Subchronic supplementation of lithium carbonate induces reproductive system toxicity in male rat

Lithium is frequently used as an effective drug for the treatment of several psychiatric disorders in human. This alkali element and its salt, at its higher doses, may lead to various side effects or has several toxic effects after prolonged therapeutic use. To test this hypothesis, the present study was designed to investigate the adverse effect of subchronic exposure of lithium carbonate on reproductive organs of male rat. Rats were exposed to lithium carbonate at doses of 500, 800, 1100 mg/kg of diet for 90 days. The weight of reproductive organs, histology of testis, epididymis, seminal vesicle, prostate, testicular interstitial fluid volume (IFV), testosterone level, sperm morphology and fertility index were analyzed. Treatment with higher doses of lithium carbonate (i.e. 800, 1100 mg/kg diet) significantly reduced testes, epididymis and accessory sex organs weights, whereas, lower dose (500 mg/kg diet) did not show any untoward effect. Similarly, the sperm number from cauda epididymis and daily sperm production was significantly decreased with higher doses of lithium carbonate. The serum testosterone levels and IFVs were also reduced significantly. Seminal vesicle and prostate secretions were completely blocked and spermatozoa were not seen in the lumen of epididymis and vas deference. Histological studies have revealed that lithium carbonate (1100 mg/kg) caused degeneration of spermatogenic cells and vacuolization of sertoli cells cytoplasm in the testis. The sperm transit rate and production of abnormal spermatozoa were significantly (P<0.01) increased. When the lithium carbonate-treated males were mated with normal cyclic females, the fertility index declined to 50% even after 30 days of withdrawal of lithium carbonate treatment. These results clearly suggest that subchronic exposure of lithium carbonate promote reproductive system toxicity and reduces fertility of male rats.     

Toxic effects of cypermethrin on the male reproductive system: with emphasis on the androgen receptor

The 15‐day intact adult male assay was used to investigate the reproductive toxicity of cypermethrin. We also evaluated the contributions of the androgen receptor (AR) to cypermethrin‐induced reproductive impairments. Sixty adult male Sprague–Dawley rats were randomly divided into five groups and treated with different doses of cypermethrin (0, 6.25, 12.5, 25 and 50 mg kg^?1 per day) by oral gavage for 15 days. After the rats were sacrificed, the testes, epididymides, seminal vesicles and prostates were excised and weighed. One testis was frozen to be used for daily sperm production. Another testis was processed for AR immunohistochemical analysis and electron microscopic observation. We found that the weights of prostates were significantly decreased in cypermethrin treatment at doses of 25 and 50 mg kg^?1 per day. Rats treated with cypermethrin at 50 mg kg^?1 per day exhibited a significant reduction in testicular daily sperm production. Seminiferous tubule changes were noted, including atrophy and distorted seminiferous tubules, reduction and deformation of spermatogonia, spermatocyte and disordered arrangement of spermatoblasts. Ultrastructural changes were found in cypermethrin‐treated groups with disrupted cellular junctions, abnormal morphology of the nucleus, necrosis of spermatogonia spermatocytes and Sertoli cells. To clarify the possible mechanism, AR expression and the serum levels of testosterone were assayed. AR levels were significantly reduced in the rats treated with cypermethrin and the serum levels of testosterone were reduced in cypermethrin treatment at a dose of 50 mg kg^?1 per day. These data suggested that cypermethrin can induce impairments of the structure of seminiferous tubules and spermatogenesis in the male rats. The impairments can be attributed to the reduced AR expression. Copyright © 2011 John Wiley & Sons, Ltd.     

Evaluation of the reproductive toxicity of patulin in growing male rats

Patulin is a mycotoxin produced by several Penicillium, Aspergillus and Byssachlamys species. Patulin can be produced on different food products including fruits, grains, cheese, cured meats, but in natural situations patulin is exclusively found in apple and apple products. Patulin, at dose of 0.1 mg/kg bw/day, was administered by gavage to the growing male rats aged 5–6 week for 60 or 90 days. At the end of the experiment, sperm counts and morphology were investigated. Also, effects of patulin on the epididymis, seminal vesicle and prostate tissues were examined histopathologically and morphologically.

While sperm counts increased in patulin-treated rats for 60 days, sperm counts in patulin-treated rats for 90 days decreased compared to the corresponding control group. Patulin affected sperm morphology of growing male rats. Tail abnormalities like bent and/or coiled tails, and sticking of sperm tails were observed. A significant change was not determined in absolute and relative weights of the seminal vesicle and prostate of patulin-treated rats. While absolute cauda epididymal weights increased in rats treated with patulin for 60 days, absolute and relative cauda epididymal weights reduced in rats treated with patulin for 90 days. In histologic examination, some histopathological changes were observed in the epididymis and prostate tissues of rats in patulin treatment groups.     

Evaluation of reproductive toxicity in rats caused by organic extracts of Jialing River water of Chongqing, China

OECD 421 screening test protocol was used to evaluate the reproductive toxicity of organic extracts of river water. These extracts, at doses of 0, 2, 16, or 80 equivalent L/kg body weight (bw), were administered to rats daily by oral gavage. Vacuole degeneration of seminiferous epithelium was observed in the dosed groups. The caudal sperm counts/epididymis weight and the percentages of sperm with abnormal heads were increased in the group dosed with 80 L/kg bw/day compared to the control group. Exposure of rats to organic extracts at the high dose resulted in a decrease in testosterone levels. The serum level of follicle-stimulating hormone increased in the groups dosed with 16 or 80 L/kg bw/day compared to the control group. The number of apoptotic spermatid increased in the dosed groups. The results suggest that the extracts cause pathological damage to testicular tissue and disruption of spermatogenesis.     

Association of methamidophos and sleep loss on reproductive toxicity of male mice

This study investigated the effects of organophosphate exposure on the male reproductive system of mice submitted to chronic sleep loss condition. Adult Swiss mice were distributed into 4 groups: control; methamidophos (MTP); sleep restriction (SR); and MTP + SR. The dose of methamidophos was 0.002 mg kg⁻¹ day⁻¹ (half of the Acceptable Daily Intake). Sleep restriction condition was 21 h day⁻¹ during 15 days. In relation to control group, MTP treatment induced a significant reduction of 12% on morphologically normal spermatozoa in both MTP and MTP + SR groups. In addition, the absolute and relative weights of the seminal vesicles were decreased (MTP, −34%; MTP + SR, −45%). Epididymal fat was reduced in SR groups (SR, −64%; MTP + SR, −58%). Plasma testosterone levels were significantly decreased in MTP and SR groups, and progesterone levels were increased 8 times in MTP + SR in comparison with the control group. The corticosterone levels were unaffected by MTP or SR conditions. Thus, low dose MTP exposure resulted in deleterious effects on the male reproductive system. Sleep loss associated with MTP potentiated the effect on steroidogenesis, mainly in terms of progesterone levels.     

Acute toxic effects of 3,3′-iminodipropionitrile on hypothalamic-pituitary-gonadal axis in male rats

Exposure to 3,3′-iminodipropionitrile (IDPN) causes persistent neurotoxicity, while its reproductive toxicity in female rats is transient, indicating that gonadotropin-releasing hormone (GnRH) neurons and gonadotrophs receive little or no damage from IDPN and that the transient gonadal toxicity may be also observed in males. To clarify these points, the acute toxic effects of IDPN on hypothalamic-pituitary-gonadal axis of male rats were examined histologically, biochemically and serologically. A single intraperitoneal injection of IDPN (1000 mg/kg body weight) induced signs of neurotoxicity within a day; nevertheless, GnRH neurons were not affected throughout the experimental period. Four days after IDPN treatment, the plasma level of testosterone but not gonadotropins decreased and active caspase 3-immunopositive spermatids increased; both parameters returned to normal levels afterwards. Data from our studies revealed that while IDPN had little or no toxic effect on GnRH neurons or gonadotrophs it was transiently toxic to gonads in both sexes.     

Protective effect of vitamin E against mercuric chloride reproductive toxicity in male mice

Mercury intoxication has been associated with male reproductive toxicity in experimental animals and mercury may have the potential to produce adverse effects on fertility in men. Vitamin E may protect against toxic effects of mercury in the liver and other tissues. To investigate the protective role of vitamin E against mercuric chloride toxicity for the testis, epididymis, and vas deferens of adult male mice, animals were treated with either mercuric chloride 1.25 mg/kg/day, vitamin E 2 mg/kg/kg, or a combination of the two treatments. Control animals were treated with water. Treatments were administered by daily gavage for 45 days. An additional group of animals treated with mercuric chloride were permitted to recover for 45 days after mercuric chloride treatments. Parameters studied included serum testosterone, epididymal sperm count, motility, and morphology, epididymal and vas deferens adenosine triphosphatase (ATPase), phosphorylase, sialic acid, glycogen and protein, testicular succinate dehydrogenase (SDH), phosphatases, cholesterol, ascorbic acid, and glutathione. Fertility was evaluated by sperm positive vaginal smears after overnight cohabitation with a female. Mercuric chloride produced a reduction in epididymal sperm count, sperm motility, and sperm viability, and there were no sperm-positive smears in this group. Biochemical tests from the male reproductive organs were also altered by mercuric chloride treatment. Coadministration of vitamin E with mercuric chloride prevented the changes in sperm and biochemical parameters and was associated with control rates of sperm positive smears after cohabitation. Animals given vitamin E with mercuric chloride also had lower concentrations of mercury in the testis, epididimyis, and vas deferens. Permitting animals to recover for 45 days after mercuric chloride treatment resulted in partial recovery of sperm and biochemical parameters. Vitamin E cotreatment has a protective role against mercury-induced male reproductive toxicity.     

Toxic effects of zearalenone and its derivatives α-zearalenol on male reproductive system in mice

The current study evaluated effects of zearalenone (ZEA) and its derivative α-zearalenol (α-ZOL) on male mouse semen quality, fertility and serum testosterone concentrations. Adult male mice were exposed to intraperitoneal (i.p.) injection of ZEA or α-ZOL at 0, 25, 50, and 75 mg/kg body weight (b.w.) daily for 7 days, and then mated with sexually mature untreated female mice. Semen quality, serum testosterone concentrations and fertility of treated mice were assessed. The results showed that the number of abnormal spermatozoa increased and the amount of live spermatozoa decreased significantly in males treated with ZEA at all doses. As well, a significant decrease in spermatozoa with integrated acrosome was observed in mice treated with 50 and 75 mg/kg b.w. α-ZOL. Significantly low pregnancy rate was observed when females were mated with ZEA or α-ZOL exposed males. Male mice exposed to ZEA had significant reductions in b.w. and relative epididymis weights. However, relative seminal vesicle weights were higher than those of controls. Conversely, significant increases in b.w. and relative preputial gland weight were observed in mice exposed to α-ZOL. Testicular and cauda epididymal sperm counts, efficiency of sperm production and serum testosterone concentrations were significantly reduced in mice treated with ZEA or α-ZOL at all doses in a dose-dependent manner. In conclusion, we demonstrate that ZEA or α-ZOL have adverse effects on reproductive system of adult male mice.     

Subchronic oral toxicity of microcystin in common carp (Cyprinus carpio L.) exposed to Microcystis under laboratory conditions

The subchronic oral toxicity of microcystin in common carp (Cyprinus carpio L.) was investigated in this study. The fish (mean body weight of 322±36 g, n=10) were orally exposed to Microcystis by feeding with bloom scum at a dose of 50 μg microcystins/kg body weight under laboratory conditions for 28 days. Growth assay results showed that microcystin could completely inhibit the growth of carp, but failed to change the fish hepatosomatic index. Ultrastructural examination by electron microscope revealed severe damage in hepatocytes derived from the treated fish. Serum biochemical assays with commercial kits indicated that alanine aminotransferase and aspartate aminotransferase activities were significantly increased as compared to control levels, but γ-glutamyl transferase, alkaline phosphatase and lactate dehydrogenase activities remained unchanged. Protein phosphatase inhibition assay revealed that the microcystin concentrations were 261.0±108.3 ng microcystin-LR equivalent/g fresh weight in hepatopancreas and 38.3±12.3 ng microcystin-LR equivalent/g fresh weight in muscle. The latter is above the limit recommended by the World Health Organization for human consumption. Therefore, we recommend that a warning system be instituted for announcing the occurrence of microcystin-producing water bloom and the possible risk of human intoxication.     

An evaluation of the male reproductive toxicity of cathinone

(−)-Cathinone is the major psychoactive component of khat plant (Catha edulis Forssk.). Khat has been shown to produce reproductive toxicity in human beings and experimental animals. However, the chemical constituents of khat leaves responsible for sexual dysfunction are not known. In the present study cathinone enantiomers have been investigated for their reproductive toxicity in rats. Cathinone produced a dose-dependent decrease in food consumption and suppressed the gain in body weight. There was a significant decrease in sperm count and motility and increase in the number of abnormal sperms in cathinone treated animals. Histopathological examination of testes revealed degeneration of interstitial tissue, cellular infiltration and atrophy of Sertoli and Leydig's cells in cathinone treated animals. Cathinone also produced a significant decrease in plasma testosterone levels of the rats. Although both enantiomers of cathinone produced deleterious effects on male reproductive system, (−)-cathinone was found to be more toxic. From this study it may be concluded that the cathinone content in khat may be partially or totally responsible for the reproductive toxicity in khat chewers.     

Immunomodulatory effects of maternal atrazine exposure on male Balb/c mice

Atrazine is a widely used herbicide applied to corn, sugar and other crops as a broad leaf weed inhibitor. Using the Balb/c mouse model, we have determined that prenatal/lactational exposure to atrazine alters adult immune function. Pregnant Balb/c dams were exposed subcutaneously for 21 days via time release pellets to 700 microg per day of atrazine beginning between days 10 and 12 of pregnancy. Prenatal/Lactational exposure caused no overt physical malformations in the offspring and had no effect on the number of litters carried to term or the litter size. Upon reaching early adulthood (approximately 3 months of age), the state of their immune system was evaluated. There were no changes in body weight or in the organ to body weight ratio of the spleen. Additionally, no changes were observed in the number of CD8+ T cell, CD4+ T cell, or B220+ B cell subpopulations in the spleen. T cell function was assessed by measuring proliferation and cytolytic activity after in vitro allogeneic stimulation. Male mice which had been prenatally/lactationally exposed to atrazine had an increase in both T cell proliferation and cytolytic activity. The humoral immune response was assessed after immunization with heat killed Streptococcus pneumoniae (HKSP). There was a significant increase in the number of HKSP-specific IgM secreting B cells in the spleen of prenatal/lactational exposed male mice. Inasmuch as atrazine is a widespread environmental contaminant, this immunopotentiation raises concerns that it may potentiate clinical diseases, such as autoimmune disease and hypersensitivity, and needs to be carefully monitored and studied.     

Raphanus sativus extract protects against Zearalenone induced reproductive toxicity, oxidative stress and mutagenic alterations in male Balb/c mice

Zearalenone (ZEN) is a non-steroidal estrogenic mycotoxin produced by several species of Fusarium in cereals and agricultural products. It has been implicated in several mycotoxicosis in farm animals and in humans. There is unequivocal evidence of reproductive toxicity of ZEN in male mice although the mechanism of action is unknown. Several reports suggest that exposure to ZEN resulted in oxidative stress, genotoxicity and perturbation of reproductive parameters. Therefore, the aim of the current study was to evaluate the protective effects of aqueous extract of Raphanus sativus growing in Tunisia against ZEN-induced reproductive toxicity and oxidative stress. Fifty male Balb/c mice were divided into five groups and treated for 28 days as follows: the control group, olive oil-treated groups, another treated with ZEN (40 mg/kg b.w), the last one treated with R. sativus extract alone (15 mg/kg b.w) and the other with ZEN + R. sativus extract. Testis samples were collected for the epididymal sperm count, testosterone concentration, and MDA level, GPx, CAT and SOD activities. Blood samples were collected for different biochemical analyses. Also, RAPD-PCR method was performed to assess the antigenotoxic effect of the extract in germ cells. The results indicated that ZEN-induced toxicological effects in accordance to those reported in the literature: decreasing in the sperm number, testosterone level and antioxidant enzyme status. The RAPD-PCR analysis revealed an alteration in the DNA bands patterns between control and ZEN-treated mice. The extract alone, rich in many antioxidant compounds, was safe and succeeded in counteracting the oxidative stress and protect against the toxicity resulting from ZEN.     

铅接触对男性生殖系统影响的研究

目的探讨化学因素中的重金属因素对男性生殖功能的影响。方法选取本市某家具厂中200名与铅长期接触超过1年的男性工人作为本次研究的观察组,另外选取本市不接触铅和其他有害物质的男性200名作为对照组。采用问卷调查和测定被试精液当中计算精子数、顶体酶活性、雄激素、促卵泡素、促间质细胞激素的含量。结果观察组中生殖症状率为28.2%,对照组为13.6%,性欲减退观察组为23.3%,对照组为10.1%,配偶流产率观察组为2.0%,对照组为8.0%,配偶早产率观察组为18.0%,对照组为9.0%,差异均有统计学意义(P<0.05)。而两组工人在阳痿和早泄方面的症状差异均无统计学意义(P>0.05);精液检查结果显示,两组患者的精子数的差异无统计学意义(P>0.05)。而在顶体酶活性、雄激素、促卵泡素、促间质细胞激素方面差异均有统计学意义(P<0.05)。结论铅接触对男性生殖系统会有一定程度的影响,对顶体的酶活性起到较为显著的作用,同时对男性性欲、勃起等性功能也会起到弱化的作用,因此提示应该对铅接触工人增加工作保护措施和改善工作条件,必要时可暂停育龄男性铅接触的工作,以增加男性工人生殖系统的健康。     

邻苯二甲酸二环己酯对雄性大鼠生殖内分泌的毒性

目的观察邻苯二甲酸二环己酯(DCHP)对雄性大鼠的生殖-内分泌毒性,探讨内分泌干扰物评价的效应终点。方法用雄性Wistar大鼠DCHP灌胃染毒,剂量分别为125、250和500 mg/(kg.d),对照组给与玉米油。观察临床症状,体重增长,血常规,血清生化,血Zn和激素以及解剖及组织病理学等指标。结果1252、50和500 mg/(kg.d)剂量组大鼠WBC数量减少,125和500 mg/(kg.d)剂量组大鼠CHO水平升高,125、250和500 mg/(kg.d)剂量组大鼠ALB水平升高,同时250和500 mg/(kg.d)剂量组A/G值增大,250和500 mg/(kg.d)剂量组血清睾酮水平降低,250和500 mg/(kg.d)剂量组血清雌激素水平升高,1252、50和500 mg/(kg.d)剂量组肝脏器系数均明显增高,250、500 mg/(kg.d)剂量组肾脏器系数增高,其他检测指标未见有明显毒理学意义的改变。结论在没有引起生殖毒性的剂量范围[(125~500 mg/(kg.d)]内,DCHP可以改变睾酮和雌激素水平,干扰生殖内分泌调节平衡。本研究结果为评价DCHP生殖内分泌毒性提供新的数据,同时为评价筛检可疑内分泌干扰物提供了效应终点。     

Toxicological review of male reproductive effects and trichloroethylene exposure: assessing the relevance to human male reproductive health

Effects of trichloroethylene (TCE) on male reproduction and fertility have been studied in mice and rats, and assessed in workers exposed to TCE. Only limited evidence exists for any male reproductive effects in rats or humans. The human studies of TCE male reproductive effects failed to provide much useful information for risk assessment. First, the TCE-specific studies are limited in group size, scope, and typically provide no data on dose, so dose–response assessment is impossible. In other studies, TCE is only one of many solvents identified in the workplace, such that the confounding exposures or lack of evidence of specific exposures make the exposure assessment useless. For TCE risk assessment, one currently must rely upon animal studies as more reliable and useful. The rat studies were generally negative, showing systemic toxicity but little or no male reproductive toxicity. The mouse studies showed various organ effects in the male reproductive system and were typically associated with increased liver weight and kidney toxicity. Enzyme induction and oxidative metabolism appear to be important in the systemic toxicity and may likewise play a role in the reproductive toxicity of TCE. Oxidative metabolites of TCE are formed in the mouse epididymis resulting in epididymal damage, and at systemically toxic high doses, TCE may adversely affect the maturation of sperm and decreasing sperm motility. Protection against systemic toxicity should also protect against adverse effects including male reproductive toxicity.     

Effects of megadoses of pyridoxine on spermatogenesis and male reproductive organs in rats

Although it has been indicated that many neurotoxicants also cause reproductive toxicity, the reproductive toxicity of megadoses of pyridoxine, which is a neurotoxicant, has not been studied. In this paper, we studied the effects of megadoses of pyridoxine on male reproductive organs. Pyridoxine hydrochloride, 125 mg/kg, 250 mg/kg, 500 mg/kg or 1000 mg/kg, daily, was intraperitoneally injected into Wistar male rats 5 days a week for 2 or 6 weeks, and its effects on the male reproductive organs were investigated. After 2 weeks of administration, absolute weights of the testis in the 500 and 1000 mg/kg epididymis in all the exposed groups and prostate gland in the 1000 mg/kg group decreased, and mature spermatid counts in the testis decreased in the 1000 mg/kg group. After 6 weeks administration, the absolute and relative weights of the testis, epididymis, prostate gland and seminal vesicle decreased in the 500 mg/kg and 1000 mg/kg groups, and mature spermatid counts in the testis and sperm counts in the epididymis decreased in these groups. Among the marker enzymes of the testicular cells, LDH-X activity decreased, and -glucuronidase activity, cytochrome P-450 content and cytochrome b5 content increased in the 1000 mg/kg group. Plasma testosterone concentration did not significantly alter in all the exposed groups. From these results, it was concluded that megadoses of pyridoxine affected the spermatogenesis and decreased reproductive organ weights in the rat.     

The effects of methyl tert-butyl ether (MTBE) on the male rat reproductive system

Methyl tert-butyl ether (MTBE) is an oxygenated compound, which has been widely used in Asia, Europe and North America. Although numerous in vitro and in vivo studies have demonstrated the carcinogenicity and the toxicity of MTBE, there is still a lack of data on reproductive system exposure of MTBE in male rodent animals. We studied subacute exposure of MTBE on the reproductive systems of male Sprague-Dawley rats. MTBE was administered to rats at dose levels of 0, 400, 800 and 1600 mg/kg/day. After 2 or 4 weeks of treatments, the rats were euthanized, and their serum, epididymis and testes were collected. Significant adverse effects in their reproductive system were observed including: a significant increase in the percentage of abnormal sperm; an irregular and disordered arrangement of the seminiferous epithelium indicated by a histopathological examination; changed serum levels of testosterone (T), luteinizing hormone (LH) and follicle stimulating hormone (FSH); and decreased levels of mRNA and of androgen binding protein (ABP). In the oxidative stress study, results indicated an increased maleic dialdehyde (MDA) content, implying a raised peroxide level, and that the total antioxidant ability in serum was significantly increased. This finding was especially strong at 1600 mg/kg/day MTBE. In the 2-week treatment, at 1600 mg/kg/day, the mRNA level of 8-oxoguanine DNA glycosidase (OGG1) was significantly decreased, and the mRNA level of the extra-cellular form of superoxide dismutase (SOD(EX)) was significantly increased. Our experiments suggest that relatively high doses of MTBE can exert reproductive system toxicity of male rats and disturb the secretions of T, LH and FSH, possibly due to oxidative stress induced by MTBE.