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.     

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.     

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.     

Protective role of propolis against reproductive toxicity of triphenyltin in male rabbits

Triphenyltin (TPT) is known to cause endocrine disruption, reproductive toxicity and a decrease in testosterone production. It is involved in the production of reactive oxygen species. Propolis has been reported to be an important antioxidant. Therefore, the present study aimed to elucidate the possible protective effects of propolis in alleviating the toxicity of triphenyltin chloride (TPTCl) on reproductive performance, testosterone levels, lipid peroxidation and enzyme activities in seminal plasma of male New Zealand white rabbits. Animals were orally administered the doses of propolis, TPTCl and propolis plus TPTCl every day for 12 weeks. Results showed that semen quality was deteriorated following treatment with TPTCl. Also, testosterone levels, body weight (BW), relative weights of testes (RWT) and epididymis (RWE) were decreased. Thiobarbituric acid-reactive substances and lactate dehydrogenase were increased, while glutathione S-transferase, transaminases and phosphatases were decreased in seminal plasma of rabbits treated with TPTCl compared to control. Propolis alone significantly increased testosterone levels, BW, RTW, REW, semen characteristics and seminal plasma enzymes, and decreased the levels of free radicals and lactate dehydrogenase. Furthermore, the presence of propolis with TPTCl alleviates its toxic effects. From the present study, it can be concluded propolis can be effective in the protection of TPTCl-induced reproductive toxicity.     

Male reproductive toxicity of four bisphenol antioxidants in mice and rats and their estrogenic effect

Male mice and rats were fed a diet containing four bisphenol antioxidants, 2,2′-methylenebis(4-ethyl-6-tert-butylphenol) (ME), 2,2′-methylenebis(4-methyl-6-tert-butylphenol) (MM), 4,4′-butylidenebis(3-methyl-6-tert-butylphenol) (BM), or 4,4′-thiobis(3-methyl-6-tert-butylphenol) (TM) at levels of 0.06–0.25% for 2 months. BM and TM decreased epididymal, seminal vesicular, prostate and preputial weights, and injured seminiferous tubules in mice in a dose-dependent fashion. BM and TM also reduced sex accessory organ weights and sperm production capacity in rats, but MM and ME were more toxic to rats than BM and TM. ME and MM did not bind ER_α up to 10⁻³ M, while BM and TM competitively bound ER_α against β-estradiol (E2). Fifty percent inhibitory concentrations (IC₅₀ s) of BM, TM, and bisphenol A (positive control) against E2-binding were 7.3×10⁻⁶ M, 1.8×10⁻⁵ M, and 1.4×10⁻⁵ M, respectively. When ovariectomized (OVX) mice were sc administered TM at doses of 60 and 300 mg/kg/day for 4 days, or when OVX mice were fed BM in the diet at a level of 0.25% for 2 months, uterine weight was significantly increased. These results suggest that BM and TM are weakly toxic, possibly through an estrogenic mechanism to male reproductive organs in mice as well as rats, while MM and ME may be the direct testicular toxins in rats but not mice. A part of this study was presented at the 74th annual meeting of the Japanese Society for Hygiene held from 24–27 March 2004 in Tokyo, Japan.     

Propolis protection from reproductive toxicity caused by aluminium chloride in male rats

Different forms of aluminium (Al) are environmental xenobiotics that induce free radical-mediated cytotoxicity and reproductive toxicity. Propolis has been reported to be important antioxidant. Therefore, this study aimed at elucidating the protective effects of propolis against reproductive toxicity of aluminium chloride (AlCl₃) in male rats. The first group served as control. Group 2 received 34 mg AlCl₃/kg bw (1/25 LD₅₀). Group 3 was administered 50 mg propolis/kg bw/day. Group 4 was treated with AlCl₃ plus propolis. Treatment was continued for 70 days. AlCl₃ caused a decrease in testes, seminal vesicle and epididymis weights, sperm concentration, motility, testosterone level and the activities of 17-ketosteroid reductase, CAT and GST, and GSH content. While, dead and abnormal sperm and testes TBARS concentrations were increased. In the AlCl₃-treated group, histopathologic examinations revealed apparent alterations in the testes, where it induced marked lesions in seminiferous tubules. Propolis alone decreased dead and abnormal sperm and TBARS, and increased testosterone, GSH, 17-ketosteroid reductase, CAT and GST. Results showed that propolis antagonized the harmful effects of AlCl₃. This was proved histopathologically by the great improvement in testes. In conclusion propolis could be effective in the protection against the reproductive toxicity of AlCl₃.     

Sensitivity of male reproductive endpoints in nonhuman primate toxicity studies: A statistical power analysis

To determine the sensitivity of male reproductive toxicity endpoints in NHPs we performed a power analysis of routine and triggered endpoints using control data from sexually mature Asian and Mauritian NHPs. The power to detect a 50% change from control was 13–30% for male reproductive organ weights, ∼30% for testicular volume, 6–66% for seminal analyses and 10–78% for male hormones. Overall, male reproductive endpoints have poor power (less than 80%) to detect a 50% change from control with a group size of 3 monkeys. Confidently identifying adverse male reproductive effects with these endpoints would likely require specialized study designs with larger group sizes. Triggering of non-routine endpoints in cases where there is special concern for male reproductive toxicity is unlikely to increase sensitivity to detect adverse effects.     

Toxic effects of Microcystis cell extracts on the reproductive system of male mice

In this paper, the reproductive toxicity of male mice treated with Microcystis aeruginosa cell extracts containing microcystins was examined. In contrast to the control group, male mice exposed intraperitoneally to 3.33 or 6.67 μg microcystins/kg body weight for 14 days had decreased mean body weight, and the mean absolute weight of the testes and epididymides was decreased. However, the mean relative weight of the testes increased compared to the controls. In addition, histological examination of microcystin-treated mice indicated that the testes were damaged and the space between the seminiferous tubules was more pronounced compared to control mice. The quality of mature sperm in the seminiferous tubules was also decreased in treated mice compared with the control group. Further studies showed that motility and viability of the sperm from microcystin-treated mice were reduced, but no significant difference was found in the concentration and abnormality of the sperm from treated mice compared to the control. This study indicated that microcystins had numerous toxic effects on the reproductive system of male mice.     

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.     

Monitoring fertility to detect toxicity to the male reproductive system

This paper describes measures of fertility for detecting toxicity to the male reproductive system. The limitations of fertility monitoring are noted as well as the advantages and disadvantages of various fertility measures. Time to pregnancy and standardized fertility ratios, two fertility measures about which more is known, are discussed in greater depth.     

Effects of heat-induced food contaminant furan on reproductive system of male rats from weaning through postpuberty

Furan (C₄H₄O) is a volatile, colorless liquid and is used in some segments of the chemical manufacturing industry. It is found in variety of foods such as coffee, jarred and canned foods that undergo heat treatment. This study was designed to investigate the effect of furan exposure on reproductive system of male rats. Three to four weeks old rats were exposed to furan at 2, 4 and 8 mg/kg/day doses by orally for 90 days. Hematology, weights, histology and morphometry of reproductive organs, serum LH and testosterone levels, sperm count and morphology and apoptosis in testis were evaluated. Slight changes were observed in hematological parameters of furan-treated rats. The weights of seminal vesicle reduced significantly whereas the weights of prostate increased significantly in the highest furan dose group. LH and testosterone levels decreased in furan-treated rats. Histological examinations have revealed that furan caused impairments in testis, epididymis and prostate gland. Furan showed no effects on sperm counts and morphology. On the other hand apoptotic cells in testis increased significantly. According to morphometrical examination, the epithelial heights and lumen diameters of the reproductive organs have changed in treatment groups. These results indicate that subchronic furan treatment induces toxicity of the male reproductive system.     

Testicular toxicity of profenofos in matured male rats

To investigate the effect of the phosphorothoate insecticide profenofos on male specific gene expression on rat testis, 16-week-old Wistar rats were orally administered at dose of 17.8 mg/kg twice weekly for 65 days. Gene expression in the testes was monitored by DNA microarray analysis and real-time RT-PCR, which revealed that genes related to steroidogenesis including cytochrome P450 17A1 (CYP17A1), steroidogenic acute regulatory protein (StAR) and CYP11A1 were significantly increased. Besides the testes were histopathologicaly examined, which revealed testicular destruction and degeneration represented by a layer of columnar epithelium, oedematous changes surrounding the seminiferous tubules besides vacuolated spermatogonial cells and more elongated Leydig cells. These data suggest that profenofos considered as one of the male reproductive toxicants. Furthermore, we propose that the above three steroidogenic-related genes and the gene of acrosomal reaction as potential biomarkers of testicular toxicity.     

羟基脲对雄性大鼠的生殖毒性

目的观察羟基脲(HU)对雄性大鼠的生殖毒性。方法雄性大鼠分别腹腔注射HU×100、200和400mg·kg-1,连续10d。末次给药后分别于d9、d23处死动物。结果停药d9时,200、400mg·kg-1组不活动精子增加明显(P<0.05或P<0.01);停药d23时,各给药组睾丸脏/体比都明显下降(P<0.05或P<0.01);400mg·kg-1组附睾脏/体比下降明显(P<0.05),并且仍然有大量不活动精子(P<0.01);200、400mg·kg-1组精子计数明显减少(P<0.01);随给药浓度增加,各组精子畸形数量增加(P<0.01)。结论雄性大鼠连续10d腹腔注射羟基脲100mg·kg-1以上,对生殖系统产生明显毒性。     

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.     

Indium acetate toxicity in male reproductive system in rats

Indium, a rare earth metal characterized by high plasticity, corrosion resistance, and a low melting point, is widely used in the electronics industry, but has been reported to be an environmental pollutant and a health hazard. We designed a study to investigate the effects of subacute exposure of indium compounds on male reproductive function. Twelve‐week old male Sprague‐Dawley rats were randomly divided into test and control groups, and received weekly intraperitoneal injections of indium acetate (1.5 mg/kg body weight) and normal saline, respectively, for 8 weeks. Serum indium levels, cauda epididymal sperm count, motility, morphology, chromatin DNA structure, mitochondrial membrane potential, oxidative stress, and testis DNA content were investigated. The indium acetate‐treated group showed significant reproductive toxicity, as well as an increased percentage of sperm morphology abnormality, chromatin integrity damage, and superoxide anion generation. Furthermore, positive correlations among sperm morphology abnormalities, chromatin DNA damage, and superoxide anion generation were also noted. The results of this study demonstrated the toxic effect of subacute low‐dose indium exposure during the period of sexual maturation on male reproductive function in adulthood, through an increase in oxidative stress and sperm chromatin DNA damage during spermiogenesis, in a rodent model. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 68–76, 2016.     

Plasma renin activity in depressed patients treated with increasing doses of lithium carbonate

Plasma renin activity (PRA) was measured in the supine position and after active upright stance in patients with endogenous depression and in a group of healthy volunteers serving as controls. In the depressed patients, PRA was further investigated in the same conditions during treatment with increasing doses of lithium carbonate.Basal PRA values were lower in depressed patients than in normal controls, particularly in the upright stance, and tended to rise gradually during lithium therapy. These findings suggest that lithium may work as a stimulant of the reninangiotensin system, and possibly as an antidepressant, by way of producing functional activation of the norepinephrine system independent of its action on the water and electrolyte balance.     

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。     

Reproductive toxicity evaluation of vanadium in male mice

The reproductive toxicity of vanadium was studied in mice. Male Swiss mice were exposed to sodium metavanadate at doses of 0, 20, 40, 60, and 80 mg/kg per day given in the drinking water for 64 days. To evaluate the fertility of the vanadium-treated animals, males were mated with untreated females for 4 days. A significant decrease in the pregnancy rate was observed at 60 and 80 mg/kg per day of sodium metavanadate. However, metavanadate did not reduce fertility in male mt 20 and 40 mg/kg per day. Reproductive toxicity was measured by sperm count, sperm motility, organ weights, and histologic evaluation of the testes. Decreased body and epididymis weight was only observed in the 80 mg/kg per day group, while testicular weights were not altered by the treatment with all doses used. Sperm coung was significantly decreased at 40, 60, and 80 mg/kg per day, but the sperm motility was unaffected. Histopathological examination revealed that the testes were normal and that the epididymis of treated male mice contained normal appearing sperm. The no observed adverse effect level (NOAEL) was 40 mg/kg per day. Consequently, vanadium would not cause any adverse effect on fertility or testicular function in male mice at the concentrations usually ingested by humansthrough the diet and drinking water.     

Developmental and reproductive toxicity evaluation of toluene vapor in the rat. I. Reproductive toxicity

The reproductive toxicity of toluene was evaluated in a 2-generation test in which male and female Sprague–Dawley rats, parental (F0) and first generation (F1), were exposed to toluene via whole body inhalation, 6 h/day, 7 days/week for 80 days premating and 15 days of mating at concentrations of 0, 100, 500 and 2000 ppm (0, 375, 1875 and 7500 mg/m³). Toluene was administered at 2000 ppm to both sexes, or to females or males only to be mated with untreated partners. Pregnant females at all dose levels were exposed from gestation day (GD) 1–20 and lactation day (LD) 5–21. At LD5, females were removed from their litters for daily exposure and returned when 6 h of exposure was completed. F1 pups selected to produce the F2 generation were treated for 80 days beginning immediately after weaning (LD21) and initially mated at a minimum of 100 days of age. F2 pups were not exposed to toluene by inhalation.

Toluene exposure did not induce adverse effects on fertility, reproductive performance, or maternal/pup behaviors during the lactation period in males and females of the parental or first generation, but did inhibit growth in F1 and F2 offspring in the 2000 ppm (both sexes treated) and 2000 ppm (females only treated) groups. Caesarean section of selected 2000 ppm (both sexes treated) dams at GD20 showed reduced fetal body weight and skeletal variations. Exposure to toluene caused decreased pup weights throughout lactation in F1 and F2 2000 ppm (both sexes treated), and 2000 ppm (females only treated) groups. Exposure at 2000 ppm to male parents only did not induce similar weight inhibition in offspring. The toluene offspring NOAEL is 500 ppm in groups in which maternal animals were exposed, and 2000 ppm for male only treated groups.     

Impairment of testicular endocrine function after lead intoxication in the adult rat

To clarify the mechanism of the action of lead on male reproductive function, adult male rats were injected intraperitoneally (i.p.) with lead acetate (8 mg/kg/day of lead), 5 days a week for 35 days. Despite this high dose, germ cells and Sertoli cells did not appear to be major targets of lead. However, lead determination in the reproductive organs showed that the accessory sex glands are such a target. Epididymal function was unchanged. In lead-exposed rats, plasma and testicular testosterone dropped by about 80%, but plasma luteinizing hormone (LH) only dropped by 32%. After luteinizing hormone releasing hormone (LHRH) stimulation of the pituitary, the plasma LH level reached the control one, but plasma testosterone remained significantly reduced by 37%. The sharp decrease in the testosterone: LH ratio in lead-exposed rats, combined with the significant reduction of intertubular tissue volume in the testes, indicate impaired Leydig cell function.