邻苯二甲酸酯类暴露致雄性生殖毒性机制的研究进展

邻苯二甲酸酯类(Phthalates,PEs)是环境内分泌干扰物(环境雌激素),其暴露与人群生活密切相关.PEs毒性持久,可作为塑化剂应用于塑料制品;但PEs与塑料高分子聚合物以键能较弱的氢键或范德华力结合,致使其易从塑料材料中逸出,经食物链富集后逐级放大,危害人体健康.据报道,我国人群总PEs的暴露水平为23 ～ 1...     

低剂量毒死蜱重复染毒诱发雄性大鼠生殖毒性及其机制

目的探讨毒死蜱(CPF)低剂量重复染毒对雄性大鼠生殖功能的影响及其可能作用机制。方法健康雄性Wistar大鼠ig给予CPF 1,5和10 mg.kg-1,每日1次。连续染毒12周后取大鼠附睾和睾丸称重计算脏器系数,进行组织病理学、精子数量以及活力及畸形率等检查,测定睾丸碱性磷酸酶(AKP)、酸性磷酸酶(ACP)、γ-谷氨酰转肽酶(γ-GT)和乳酸脱氢酶(LDH)的活性;TUNEL法检测细胞凋亡,免疫组化及Western印迹法检测胱天蛋白酶和Fas,FasL蛋白的表达。结果与正常对照组相比,CPF染毒大鼠睾丸脏器系数显著升高,精子数及精子活力降低,精子畸形率显著升高(P<0.05),睾丸AKP和γ-GT活性抑制明显。组织病理检查显示,睾丸曲细精管疏松和生精细胞减少。CPF染毒组生精细胞凋亡增加(P<0.05)。Fas/FasL蛋白表达量升高。结论 CPF低剂量重复染毒能够诱导雄性大鼠生殖毒性,其作用机制可能与激活Fas/FasL受体途径而引起睾丸生精细胞凋亡有关。     

砷的雄性生殖毒性研究进展

砷是一种天然类金属化学元素,广泛存在于自然界中[1].同时,砷也是一种雄性生殖毒物,可影响下丘脑—垂体—睾丸轴、损害支持细胞和生精细胞,引起精子质量下降[2].本文就长期砷暴露所引起的雄性生殖毒性及相关机制进行综述. 1砷的雄性生殖毒性 1.1砷对下丘脑—垂体—睾丸轴的影响下丘脑—垂体—睾丸轴是男性生殖的重要调节路径,...     

邻苯二甲酸酯类化合物的雄性生殖毒性

邻苯二甲酸酯类化合物(PAEs)属于芳香族二羧酸酯,多为高沸点、低蒸气压液体,对塑料的稳定性起着重要作用,广泛用作多种塑料膜的增塑剂,特别用于纤维素与乙烯树脂,以增加其韧性和柔性。鉴于食品包装的需要,其中许多已做过急性毒性及慢性饲养试验,其毒性均较低 1978年美国国际商业局公布的PAEs产量约为200万吨。1987～1989年我国平均年产量约为18万     

雄性生殖毒性评价体系及完善

人类工业文明在开拓大自然取得长足进步的过程中,所产生的各种副产品对人类的生殖健康也产生一系列的负面影响,精子数量下降,精液体积减少,生殖器官畸形、精子质量下降和生育力降低问题日益增多。如何有效评价外源物质对雄性生殖系统的潜在毒性,这是一个问题。系统评价一个外源     

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。     

美他多辛对雄性大鼠的生殖毒性

美他多辛 (Metadoxine ,MTDX)是意大利 80年代上市的一种代谢平衡药 ,它能减轻乙醇戒断综合征及早期标志物氨的排除 ,是目前临床用于治疗化学性和乙醇性肝病的药物[1 3 ] 。MTDX化学名称为吡哆素L 2 吡咯烷酮 5 羧酸酯 ,吡哆素是维生素B6由吡哆醇 (PN)、吡哆醛 (PL)和吡哆胺组成 ,L 2 吡咯烷酮 5 羧酸酯俗称L 焦谷氨酸 (L 2 Pyrrolidone 5 carboxylate ,L PCA) ,MTDX由二者 1∶1聚合而成 ,是 1对离子 ,在体内又分解成这 2种离子。目前 ,国内外对于MTDX的报道仅见于其药效机制方面 ,未见其对雄性生殖系统毒性作用及其机…     

镉的雄性生殖毒性与颌下腺-性腺轴的关系

镉(Cadmium，Cd)是有毒重金属，广泛应用于半导体、电池等工业。镉对人体的危害主要来源于工农业生产所造成的环境污染。随着工农业生产的发展，受污染环境中的镉含量也逐年上升。镉在体内的生物半衰期长达30年，为已知的最易在体内蓄积的毒物。近年来，镉消费模式发生了改变，以前大量用于电镀的镉，现在更多的用于电池和电子业，致使回收困难，更增加了环境污染的程度。吸烟引起的镉损伤也日益引起社会关注。     

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.     

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.     

Heavy metal and metalloid - induced reproductive toxicity

Heavy metals and metalloid exposure are among the most common factors responsible for reproductive toxicity in human beings. Several studies have indicated that numerous metals and metalloids can display severe adverse properties on the human reproductive system. Metals like lead, silver, cadmium, uranium, vanadium, and mercury and metalloids like arsenic have been known to induce reproductive toxicity. Moderate to minute quantities of lead may affect several reproductive parameters and even affect semen quality. The ecological and industrial exposures to the various heavy metals and metalloids have disastrous effects on the reproductive system ensuing in infertility. This work emphasizes the mechanism and pathophysiology of the aforementioned heavy metals and metalloids in reproductive toxicity. Additionally, this work aims to cover the classical protective mechanisms of zinc, melatonin, chelation therapy, and other trending methods to prevent heavy metal-induced reproductive toxicity.     

附子提取物的大鼠生殖毒性研究

目的：探讨附子提取物对雌性大鼠生殖毒性的影响。方法附子提取物给大鼠连续灌胃30 d,考察脏器指数、动情期观察、生殖激素含量变化。结果附子提取物造成雌性大鼠动情周期紊乱,脏器指数明显下降,性激素：卵泡刺激素（FSH）、黄体生成素（LH）、雌二醇（E2）、孕酮（P）含量较阴性对照组均显著下降。结论附子提取物的生殖毒性作用可能与FSH、LH、E2、P含量下降有关,提示提高性激素水平,可有助于降低附子提取物的生殖毒性。     

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.     

Reproductive toxicity on female mice induced by microcystin-LR

There are increasing concerns about health risk of human exposure to microcystin-LR (MC-LR) over the past few decades. Nevertheless, its female mammalian reproductive toxicity has not been addressed yet. In the present study, we firstly reported MC-LR could impact female reproductive function of mammals. After 28 days MC-LR exposure, relative ovary weight significantly reduced in 20 μg/kg MC-LR group and this reduction may be relative with pathomorphological changes of ovary. The result of histological evaluation of follicles showed that primordial follicles decreased roughly in half at high dose level compared with control. Since serum hormone assay indicated that MC-LR induced decrease of progesterone but not FSH or LH, disturbance of estrus cycle was seemed to result from direct impact of ovary rather than indirectly from hypothalamus or pituitary. As expected, MC-LR was detected in the ovaries of MC-LR exposure mice by immunoblot analysis.     

S1P致环磷酰胺染毒后雄性小鼠凋亡蛋白表达的影响

目的 探讨1-磷酸鞘氨醇(S1P)对雄性小鼠生殖细胞毒性损害的拮抗机制.方法 健康雄性昆明小鼠40只,随机分为5组,即正常对照组;S1P低剂量(0.5 μg/10 g小鼠体质量)、中剂量(1.0 μg/10 g小鼠体质量)、高剂量(2.0 μg/10 g小鼠体质量)组;环磷酰胺染毒组.腹腔注射给药5d,于首次给药后30 d处死.分别采集睾丸样本,小鼠睾丸病理切片观察睾丸组织的病理学改变,免疫组化检测小鼠睾丸凋亡蛋白Bcl-2、Bax、Caspase3的表达.结果 与环磷酰胺染毒组相比:各S1P剂量组病理学结构均有不同程度的改善,Bcl-2蛋白表达增强,Bax、Caspase-3蛋白表达减弱.经图像分析软件分析后得出平均光密度值,各实验组与染毒组相比差异有统计学意义(P＜0.05).结论 S1P对雄性小鼠生殖细胞毒性损害具有一定的拮抗作用,可能通过活化Bcl-2和抑制Bax,抑制下游Caspase-3的表达来拮抗环磷酰胺所致的生殖毒性.     

Reproductive toxicity of melamine against male mice and the related mechanism

Melamine is a nitrogen-containing heterocyclic organic compound with a triazine skeleton, which has been widely applied in industrial and chemical fields. Previous toxicity studies of melamine mainly focused on renal toxicity and hepatic pathological changes, but its toxicity against the reproductive system has seldom been assessed. We investigated the effects of melamine on the reproductive system of male mice. Forty healthy male Kunming mice were randomly divided into a normal saline negative control group, a low-dose melamine group, a medium-dose melamine group and a high-dose melamine group (n?=?10). The mice were administered for five consecutive days and killed on the 35th day after first administration. In melamine administration groups, seminiferous tubules had disordered, loose arrangement, and spermatogenic cells at all levels obviously decreased. The sperm count and motility decreased significantly, and the sperm deformity rate increased significantly. Melamine induced apoptosis of testicular spermatogenic cells. To further explore the mechanism, we detected metabolism-related enzymes sorbitol dehydrogenase (SDH) and lactate dehydrogenase (LDH) as well as oxidative stress indices superoxide dismutase (SOD) and malondialdehyde (MDA). The activities of SDH, LDH and SOD in melamine treatment groups decreased significantly, and the MDA level increased obviously. The expressions of apoptosis-related proteins Bcl-2, Bax and caspase-3 were detected by immunohistochemistry. The expression of Bcl-2 significantly increased, but those of Bax and caspase-3 significantly reduced (p?相似文献   

匹多莫德的生殖毒性实验研究

目的研究匹多莫德(pidotimod,PDM)对实验大鼠在致畸敏感期的生殖毒性。方法健康Wis-tar雌性受孕大鼠,于受孕后5~15d灌胃给予200、4008、00mg/kg的匹多莫德,至受孕后20d处死动物,检测各项指标,对匹多莫德的致畸敏感期生殖毒性进行评价。结果口服匹多莫德200、4008、00mg/kg后,匹多莫德对受孕大鼠的黄体数、着床率、胎儿数、胎儿体重及性别、胎儿内脏及骨骼检查等各项检测指标均无明显变化,同对照组比较差异无统计学意义。结论匹多莫德在本实验所用剂量时无致畸作用,这种用于大鼠的剂量,相当于该药的人用最大剂量的8倍、16倍、32倍,所以人用此药是安全的。     

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.