乙醇对大鼠生殖内分泌系统影响

乙醇对大鼠生殖内分泌系统影响崔金山陈露秋张玉敏马明月（沈阳医学院预防医学系，沈阳１１００３１）选用健康成熟的体重１８０－２４０ｇ的雄性Ｗｉｓｔａｒ大鼠１００只，随机分为阴性对照组，５００，１０００，１５００和２５００ｍｇｋｇ－１ｉｇ乙醇染毒组，每组２...     

丹参酮对更年期大鼠生殖内分泌系统的影响

目的 观察丹参酮对更年期大鼠生殖内分泌系统的影响。方法 以更年期大鼠为模型，观察丹参酮对更年期大鼠子宫、卵巢、肾上腺脏器系数的影响，用放免试剂盒检测血清雌二醇（E2）、促卵泡激素（FSH）、黄体生成素（LH）的含量。结果 更年期大鼠经灌胃给予丹参酮后，提高了子宫、卵巢、肾上腺等脏器系数，提高了其降低的E2，降低了去卵巢大鼠升高的FSH和LH。结论 丹参酮对更年期大鼠的生殖内分泌系统功能紊乱有较好的调节作用。     

壬基酚对SD雄性大鼠生殖功能的影响

壬基酚 (ｎｏｎｙｌｐｈｅｎｏｌ,ＮＰ)是合成壬基酚聚氧乙烯醚 (ｎｏｎ ｙｌｐｈｅｎｏｌｐｏｌｙｅｔｈｏｘｙｌａｔｅｓ,ＮＰＥｓ)所需要的基本成分 ,壬基酚聚氧乙烯醚作为非离子表面活性剂被广泛应用于洗涤剂、乳化剂、造纸工业[1 ] 。ＮＰＥｓ在环境中降解产生壬基酚。由于ＮＰ的高度疏水性 ,使得其易于在水体下的淤泥中浓集 ;而在厌氧环境下 ,ＮＰ相当稳定 ,不易降解。所以造成ＮＰ在水环境中广泛分布。 2 0世纪 90年代以来 ,由于发现一些国家人群中精子数在过去 5 0年中普遍降低 ;某些水生物 (如 :鳄鱼、龟等 )和鸟类的性别畸形发生…     

男性生殖内分泌系统调节的研究进展

男性的主要生殖器官为睾丸和附属性器官。睾丸由曲细精管和间质细胞构成，其主要功能是产生精子、分泌以睾酮为主的雄性激素。睾酮通过和靶细胞内的雄激素受体结合对机体产生一系列的生理调控作用。除睾酮外，间质细胞刺激素、卵泡刺激素、抑制素等生殖激素以及雄激素受体对维持男性正常的生殖功能起着重要的作用。     

米非司酮对女性生殖内分泌系统的影响

米非司酮是一种抗孕激素类药物,最初用于抗早孕、药物流产、紧急避孕等,后来随着对其作用机理的进一步探讨,发现米非司酮具有抗雌激素样作用,被用来治疗雌激素依赖性疾病和肿瘤,如子宫肌瘤、子宫内膜异位症、乳腺癌、子宫内膜癌等。在治疗过程中发现连续应用米非司酮可引起闭经,故认为米非司酮对生殖内分泌轴有一定影响。本文就米非司酮对生殖内分泌系统的影响作一综述。     

甲基苯丙胺对泌尿生殖内分泌系统影响的研究进展

甲基苯丙胺(俗称冰毒)是目前新型合成毒品中的主要品种。滥用甲基苯丙胺不仅影响个体身心健康,也给社会安全带来威胁。泌尿生殖内分泌系统对人体的内环境调节、激素分泌、生殖及性功能等发挥着至关重要作用。研究报道甲基苯丙胺可不同程度影响泌尿生殖内分泌系统的相关器官组织包括肾上腺、肾脏、性腺(睾丸或卵巢)、子宫和阴茎。探讨其影响机制利于缓解毒品滥用者的症状,维持机体内环境稳定和控制不良行为。     

雷公藤多苷对女性生殖内分泌系统的影响

雷公藤多苷(GTW)是一种临床应用广泛的免疫抑制剂,对女性生殖系统功能有明显抑制作用。本文主要从GTW的生殖抑制作用研究概况,及研究中存在的分歧等方面进行综述,以期为GTW的进一步药理研究及临床应用提供参考。     

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。     

乙二醇对雄性大鼠生殖系统的影响

Wistar雄性大鼠,乙二醇连续灌胃染毒13周,剂量分别为333、666、1332和2664mg/kg。结果表明,与对照组比各剂量组的活动精子百分率明显降低,精子畸形率明显增加(P<0.01);666mg/kg组大鼠的肾脏脏器系数明显高于对照组(P<0.05);1332mg/kg组雄性大鼠的交配率、生育指数明显下降(P<0.05),血清睾丸酮和LH水平明显降低(P<0.01),对睾丸和前列腺有明显影响,生长明显受抑;2664mg/kg组除以上指标改变外,精子数明显减少,胎吸收率非常明显升高,各组的FSH水平变化不明显。对雄性大鼠生殖系统无作用剂量、阈剂量和明显作用剂量分别为333m、666m和1332mg/kg。     

氯解磷定在急性辛硫磷中毒大鼠体内药代动力学

目的　探讨氯解磷定 (PAM Cl)在急性辛硫磷中毒大鼠体内药代动力学性质变化和PAM Cl对乙酰胆碱酯酶 (AChE)的复能作用 ,为治疗辛硫磷中毒合理利用PAM Cl提供科学依据。方法　给大鼠腹腔注射 80mg kgPAM Cl,采用高效液相色谱法测定PAM Cl血浆浓度。PAM Cl的血药 时间曲线用 3P97拟合。改良Ellman法测AChE活力。结果　PAM Cl在急性辛硫磷中毒大鼠和正常大鼠体内血药浓度经时过程均符合一室开放模型。与正常大鼠相比 ,PAM Cl在急性辛硫磷中毒大鼠体内血药最高峰浓度〔(2 2 85± 2 5 5 ) μg ml〕和血药 时间曲线下面积〔(13 0 4 0 2± 10 9 87) μg (min·ml)〕明显增高 (P <0 0 5 ) ,全身清除率〔(0 0 6± 0 0 1)L (min·kg)〕和中室表观分布容积〔(2 66± 0 3 7)L kg〕显著降低 (P <0 0 5 )。结论　PAM Cl在急性辛硫磷中毒大鼠体内的排泄较正常大鼠慢。     

Effects of chronic valproate treatment on reproductive endocrine hormones in female and male Wistar rats

Valproate (VPA) has been claimed to induce endocrine disorders in both sexes in humans. There is sparse information regarding the mechanisms behind these disturbances. By using an animal model, we wanted to study the effect of valproate on hormonal function in non-epileptic rats. Female rats were given 0 (vehicle control, n=15), 200 mg/kg (n=15), or 300 mg/kg (n=20) valproate twice daily by gavage for 90 days, resulting in mean valproate concentrations within the therapeutic range 4–6 h after the last dose given. Serum testosterone concentrations remained unchanged, while estradiol levels were significantly reduced in both treatment groups, leading to significantly increased testosterone/estradiol ratios. Follicle stimulating hormone (FSH) levels remained unaltered in valproate treated rats, whereas the luteinizing hormone (LH) concentrations were reduced at the lowest valproate dose. Male rats received 0 (vehicle control, n=15), 200 mg/kg (n=15), or 400 mg/kg (n=20) valproate twice daily by gavage for 90 days, resulting in mean valproate concentrations within the therapeutic range 4–6 h after the last dose. Serum testosterone levels were not significantly changed, but there was a highly significant increase in FSH and LH concentrations at the high dose. In conclusion, the study demonstrates a drug-induced effect of valproate on endocrine function in both male and female rats. The results indicate that the drug exerts its effect primarily at the gonadal level, although a centrally mediated effect cannot be ruled out.     

ARTPQ对雌性大鼠生殖内分泌影响

目的 研究新一代青蒿素抗疟药物ARTPQ重复给药对雌性大鼠生殖内分泌的影响。方法 Wistar大鼠随机分4组,对照组和ARTPQ低、中、高剂量组（35、70、120 mg/kg）,每组15只,ig给药14 d。给药后每天测量大鼠动情周期,给药结束后采集大鼠血液,Elisa方法检测大鼠血液雌激素、肾上腺皮质激素水平,肉眼观察各脏器变化及称量大鼠子宫、卵巢、肾脏及肾上腺的质量。结果 连续给药3 d后大鼠动情周期紊乱（维持于动情后期或间期）,大鼠子宫未见有扩张,平均质量低于对照组。ARTPQ低、中、高剂量组大鼠肾上腺系数高于对照组（P<0.05、0.01）。ARTPQ高剂量组大鼠雌激素水平低于对照组（P<0.05）,而ARTPQ低、中、高剂量组大鼠肾上腺素水平高于对照组（P<0.05、0.01）。结论 ARTPQ作用于肾上腺,肾上腺增生,肾上腺皮质激素的水平升高,雌激素水平降低,表现为大鼠发情周期的紊乱。     

Effects of chlorpyrifos on reproductive toxicology of male rats

The aim of this study is to investigate the effects of subchronic exposure to chlorpyrifos on reproductive toxicology of male rats. Forty healthy male rats were divided into four groups: three exposure groups and a control group. Chlorpyrifos was administered orally to male rats at 0, 2.7, 5.4, and 12.8mg/kg for 90 days to evaluate the toxic alterations in testicular histology, testicular marker enzyme activities and related genes expression levels, sperm dynamics, and testosterone levels. The body weight and the testis weight of animals did not show any significant changes. Chlorpyrifos brought about marked reduction in testicular sperm counts, sperm motility, and significant growth of sperm malformation rate in exposed males. Histopathological examination of testes showed mild to severe degenerative changes in seminiferous tubules at various dose levels. The levels of testosterone (T) showed a decreasing tendency, and there was a statistical difference between the 5.4, 12.8 mg/kg groups, and the control group. The levels of follicle stimulating hormone (FSH) were significantly increased in 5.4 and 12.8 mg/kg groups, but there were no obvious effects on the levels of luteinizing hormone (LH) and estradiol (E₂). A significant increase in the activities of LDH and LDH‐x was observed in chlorpyrifos exposed rats in 5.4 and12.8 mg/kg groups, but the expression levels of related genes had no significant differences between chlorpyrifos exposure groups and the control group. These results suggest that chlorpyrifos has adverse effects on reproductive system of male rats. © 2013 Wiley Periodicals, Inc. Environ Toxicol 29: 1083–1088, 2014.     

Human exposure to endocrine disrupting chemicals: effects on the male and female reproductive systems

Endocrine disrupting chemicals (EDCs) comprise a group of chemical compounds that have been examined extensively due to the potential harmful effects in the health of human populations. During the past decades, particular focus has been given to the harmful effects of EDCs to the reproductive system. The estimation of human exposure to EDCs can be broadly categorized into occupational and environmental exposure, and has been a major challenge due to the structural diversity of the chemicals that are derived by many different sources at doses below the limit of detection used by conventional methodologies. Animal and in vitro studies have supported the conclusion that endocrine disrupting chemicals affect the hormone dependent pathways responsible for male and female gonadal development, either through direct interaction with hormone receptors or via epigenetic and cell–cycle regulatory modes of action. In human populations, the majority of the studies point towards an association between exposure to EDCs and male and/or female reproduction system disorders, such as infertility, endometriosis, breast cancer, testicular cancer, poor sperm quality and/or function. Despite promising discoveries, a causal relationship between the reproductive disorders and exposure to specific toxicants is yet to be established, due to the complexity of the clinical protocols used, the degree of occupational or environmental exposure, the determination of the variables measured and the sample size of the subjects examined. Future studies should focus on a uniform system of examining human populations with regard to the exposure to specific EDCs and the direct effect on the reproductive system.     

Effects of environmental endocrine disruptors,including insecticides used for malaria vector control on reproductive parameters of male rats

The male reproductive system is sensitive to endocrine disrupting chemicals (EDCs) during critical developmental windows. Male Sprague-Dawley rats were exposed in utero-, during lactation- and directly to 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT), 1,1,-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE) and a mixture of DDT, deltamethrin (DM), p-nonylphenol (p-NP) and phytoestrogens, at concentrations found in a malaria-area. After dosing for 104 days, histological assessments and reproductive-endpoints were assessed. The anogenital distance (AGD) (P = 0.005) was shorter in the mixture-exposed group, while the prostate mass (P = 0.018) was higher in the DDT-exposed group. A higher testicular mass and abnormal histology was observed in the DDT-(P = 0.019), DDE-(P = 0.047) and mixture-exposed (P < 0.005) groups. This study shows that in utero-, lactational- and direct exposure to EDCs present in a malaria-area negatively affects male reproductive parameters in rats. These findings raise concerns to EDC-exposures to mothers living in malaria-areas and the reproductive health of their male offspring.     

Effects of methylmercury on male reproductive functions in Wistar rats

In this study we investigated the effects of subacute exposure to methylmercury (MeHg) on male reproductive functions in rats by means of determination of alterations in structural and functional parameters. Adult male Wistar rats received 0, 0.5, 1.0 or 3.0 mg/kg/body weight/day orally, daily MeHg for 14 days. Sperm motility, the relative sperm count and transit time in the caput/corpus epididymis, were all reduced at all doses. The lowest dose increased the number of sperm head abnormalities; daily sperm production was elevated at the intermediate dose; while at the highest dose there was a decrease in serum testosterone levels and a rise in mercury (Hg) content in reproductive organs, liver and kidneys. In conclusion, MeHg exposure produced damages on male reproductive functions which may be attributed, at least in part, to the reduction in serum testosterone levels. These consequences could potentially result in infertility in rats.     

Effects of valproic acid on fertility and reproductive organs in male rats

Crj:CD(SD)IGS rats were orally administered valproic acid at doses of 250, 500 or 1000 mg/kg/day for 4, 7 or 10 weeks. At each dose, one group of male rats was euthanized after 4-week dosage (4-week dose group) and the other two were mated with untreated females after 4 (7-week dose group) or 7 (10-week dose group) weeks of treatment with valproic acid and their fertility was evaluated. Females were euthanized on day 14-17 of gestation, and numbers of corpora lutea, implantations and live and dead fetuses were recorded. After 4, 7 or 10 weeks of treatment, males were euthanized, genital organs were weighed, the number of sperm in the cauda epididymis was counted, sperm motion analyzed, and histopathological examination of testes performed. The male rats of the 1000 mg/kg dose group died or were moribund 3 or 4 days after the start of treatment. No effects on fertility of male rats were observed up to the 500 mg/kg 10-week dose group. Treatment for 4 weeks at 500 mg/kg/day decreased epididymis weight. After 7 weeks at 500 mg/kg/day, the weights of epididymis, seminal vesicles and prostate were decreased, and the number of sperm heads per cauda epididymis and percentage of motile sperm were reduced. In the 500 mg/kg 10-week dose group, the weight of testis was decreased. On histopathological examination of the testis, degeneration of seminiferous tubules and loss or exfoliation of spermatids were observed, and the ratio of retention of step 19 spermatids in stage IX-XI was increased in the 500 mg/kg 4-, 7- and 10-week dose groups. These results suggest that analysis of sperm motion and histopathological evaluation of testes are sensitive methods for assessing toxicity of valproic acid on male reproductive organs.     

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.     

Long-term mequindox treatment induced endocrine and reproductive toxicity via oxidative stress in male Wistar rats

Mequindox (MEQ) is a synthetic antimicrobial chemical of quinoxaline 1, 4-dioxide group. This study was designed to investigate the hypothesis that MEQ exerts testicular toxicity by causing oxidative stress and steroidal gene expression profiles and determine mechanism of MEQ testicular toxicity. In this study, adult male Wistar rats were fed with MEQ for 180 days at five different doses as 0, 25, 55, 110 and 275 mg/kg, respectively. In comparison to control, superoxide dismutase (SOD), reduced glutathione (GSH) and 8-hydroxydeoxyguanosine (8-OHdG) levels were elevated at 110 and 275 mg/kg MEQ, whereas the malondialdehyde (MDA) level was slightly increase at only 275 mg/kg. Furthermore, in LC/MS-IT-TOF analysis, one metabolite 2-isoethanol 4-desoxymequindox (M11) was found in the testis. There was significant decrease in body weight, testicular weight and testosterone at 275 mg/kg, serum follicular stimulating hormone (FSH) at 110 and 275 mg/kg, while lutinizing hormone (LH) levels were elevated at 110 mg/kg. Moreover, histopathology of testis exhibited germ cell depletion, contraction of seminiferous tubules and disorganization of the tubular contents of testis. Compared with control, mRNA expression of StAR, P450scc and 17β-HSD in testis was significantly decreased after exposure of 275 mg/kg MEQ while AR and 3β-HSD mRNA expression were significantly elevated at the 110 mg/kg MEQ group. Taken together, our findings provide the first and direct evidence in vivo for the formation of free radicals during the MEQ metabolism through N → O group reduction, which may have implications to understand the possible mechanism of male infertility related to quinoxaline derivatives.     

Effects of bisphenol A given neonatally on reproductive functions of male rats

Male Sprague-Dawley rats (Crj:CD (IGS) were treated neonatally with bisphenol A (BPA) to evaluate effects on reproductive parameters. Animals were given BPA subcutaneously in corn oil to dosages of 0.002-97 mg/kg body weight, or 0.9 mg/kg 17beta-estradiol (E2) once a day from postnatal day (PND) 0 to PND 9. Preputial separation, copulatory rate, fertility rate, sperm analysis, serum testosterone levels, and gene expression in the testis were assessed. Males in the E2 group showed a decrease in testis weight and alterations of estrogen-mediated gene expression in the testis on PND 10, and by PND 150 incomplete preputial separation, decreases in the copulatory rate, testicular and accessory organ weights and number of sperm. In contrast, males in all BPA groups showed normal reproductive parameters. These results indicate that in male rats, BPA given during the neonatal period neither affected reproductive function nor evoked estrogen-mediated gene responses in the testis.