DHPO生殖毒性的毒理学评价

目的研究1，2-二甲基-3-羟基-4-吡啶酮（DHPO）的急性毒性及不同剂量、不同时间的生殖毒性。方法以昆明种近交小鼠为实验对象．首先进行半数致死量（LD50）实验，然后对DHPO低（1／8LD50）、中（1／4LD50）、高（1／2LD50）剂量组染毒小鼠进行精子畸变率观察。结果DHPO染毒小鼠经口LD50为562．34mg／kg.精子畸变实验显示，1／8LD50组、1／4LD50组与阴性对照组比较，在第14．28，35，42，70d观察，差异均无统计学意义（P〉0．05）；1／2LD50组与阴性对照组比较，在第14，28，35d观察．差异均有统计学意义（P〈0．05），而在第42，70d观察，差异无统计学意义（P〉O．05）。结论DHPO的低（1／8LD50）、中（1／4LD50）剂量未显示有生殖毒性，高剂量（1／2LD50）具有一定生殖毒性。但可在42d后恢复。     

Developmental toxicology of cadmium in living embryos of a stable transgenic zebrafish line

The toxic effects of cadmium and other heavy metals have been well established, and many of these and other environmental pollutants are known to be embryotoxic or teratogenic. However, it has proven difficult to identify individual cells that respond to toxicants among the wide range of cell populations in an intact animal, particularly during early development when cells are continually changing their molecular and physiologic characteristics as they differentiate. Here we report the establishment of an in vivo system that uses hsp70 gene activation as a measure of cadmium toxicity in living early larvae of transgenic zebrafish carrying a stably integrated hsp70-enhanced green fluorescent protein (eGFP) reporter gene. We demonstrate that eGFP expression in this strain of fish acts as an accurate and reproducible indicator of cell-specific induction of hsp70 gene expression. Furthermore, the transgene responds in a dose-dependent manner at concentrations similar to those observed for morphologic indicators of early-life-stage toxicity and is sensitive enough to detect cadmium at doses below the median combined adverse effect concentration and the median lethal concentration. The stable nature of this transgenic line should allow for extremely rapid and reproducible toxicologic profiling of embryos and larvae throughout development.     

二甲苯对雄性小鼠生殖功能的影响

小鼠吸入8.5g/m~3浓度的二甲苯,引起小鼠精子数量减少,活动精子率降低,精子畸形率增高,使小鼠致孕能力降低。由此表明,二甲苯对雄性小鼠生殖功能有一定影响。     

敌百虫暴露对小鼠及胎鼠生殖发育影响

目的研究母鼠器官形成期经口暴露较低浓度的有机磷农药-敌百虫,对母鼠生殖功能、内分泌功能及胚胎发育的影响。方法孕鼠随机分为对照组和3个实验组,在胎儿器官形成期即妊娠第6～15d经口灌胃染毒敌百虫,剂量分别为0,12.5,25和50 mg/kg。在妊娠第17d经眼球取血后处死孕鼠,研究在本实验剂量下,敌百虫对孕鼠生殖功能、内分泌功能以及胚胎发育的影响。结果（1）母鼠器官形成期经口暴露敌百虫,可导致各实验组胎鼠外观畸形发生率显著增高（P〈0.01）。（2）各剂量敌百虫暴露对孕鼠的生育力及妊娠结局无明显影响,表现在孕鼠的体重、卵巢脏器系数、胎盘脏器系数、黄体数、着床率、活胎数、死胎数、吸收胎数等与对照组比较差异无统计学意义（P〉0.05）;（3）除50mg/kg剂量敌百虫的暴露可引起母鼠血清雌二醇浓度下降外,其他各剂量组母鼠血清和卵巢的雌二醇浓度均未见明显影响。结论在本实验剂量下,器官形成期雌鼠经口暴露敌百虫对子代胚胎的生长发育有影响,表现为胎鼠的畸形发生率增加,但对母鼠的生殖功能、内分泌功能未见明显影响。     

转基因雄性小鼠不育原因分析

目的研究转基因雄性小鼠不育的主要原因。方法以野生型C57BL／6J作为对照，比较检测健康性成熟雄性转基因小鼠的睾丸、附睾、前列腺、提肛肌的脏器系数和精子数、精子活动度、活精率、精子畸形率；观察睾丸组织病理学变化及睾丸组织葡萄-6-磷酸脱氢酶（G-6-PD）、乳酸脱氢酶（LDH）、乳酸脱氢酶同工酶（LDH-X）及琥珀酸脱氢酶（SDH）的活性。结果与正常非转基因对照鼠相比，转基因鼠睾丸的脏器系数与正常对照鼠相接近，附睾、提肛肌的脏器系数显著降低。精子数、直线运动精子数显著降低（P〈0．01）；转基因鼠睾丸组织曲细精管变薄，生精细胞排列不整齐，层次减少（2层），上皮部分有变性，精原细胞、初级精母细胞分裂异常，精子形成减少；G-6-PD、LDH、LDH-X及SDH的活性均显著低于对照鼠。结论外源基因整合后，引起睾丸组织酶活性下降，影响各细胞的生理、生化功能，进而引起睾丸发育严重障碍，精子减少和活动能力降低而导致不育。     

Experimental and clinical studies on the reproductive toxicology of 2,3,7,8-tetrachlorodibenzo-p-dioxin

The reproductive toxicology of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been studied in animal models and in human populations. In animals, TCDD has a range of toxic effects on organs of the reproductive system in males and females, on hormone biochemistry, and on embryo-fetal development. These effects may involve in part an identified intracellular TCDD receptor and its association with the induction of microsomal cytochrome P-450-dependent monooxygenases in many organs. TCDD treatment increases activity of monooxygenase enzyme in liver and gonads of treated animals, but unlike other polycyclic aromatic hydrocarbons that are monooxygenase inducers, TCDD is not cytotoxic to any population of oocytes in the mature female mouse. Epidemiological studies of TCDD reproductive toxicity have been limited in design. There are some reports of adverse effects in the Seveso population and in children born to American veterans presumed to have been exposed to TCDD in Agent Orange during the Vietnam war. Occupational cohorts have not been found to show such paternally mediated effects of TCDD exposure.     

醋酸铅对雄性小鼠生殖功能的影响

给雄性小鼠灌胃染毒醋酸铅 10mg/kg、 2 0mg/kg和 40mg/kg ,每天 1次连续 3 5d。应用分光光度法测定血清和睾丸中酶活性 ,按标准方法测定小鼠生育力 ,并对睾丸、附睾进行组织病理学检查。结果表明 ,雄鼠受精率、雌鼠妊娠率、平均每窝活胎率及睾丸匀浆中的 β G和LDHx随染毒剂量增加而降低 ,死胎率和吸收胎率随染毒剂量增加而升高 ,与阴性对照组比较差异均有显著性 (P <0 0 5 ) ,并呈现明确的剂量 反应关系 ,r值依次为 -0 412、 -0 42 0、-0 5 3 7、 -0 5 3 8、 -0 617、 0 5 42和 0 5 3 5。雄鼠交配率 ,血清和睾丸匀浆中G 6 PD、ACP、LDH仅在 40mg/kg组与阴性对照组比较差异有高度显著性和显著性 (P <0 0 1或P <0 0 5 )。说明染毒醋酸铅≥ 2 0mg/kg剂量可损害雄性小鼠生殖功能。     

The cholesterolaemic effects of dietary fats in cholesteryl ester transfer protein transgenic mice.

In order to investigate the role of cholesteryl ester transfer protein (CETP) in the cholesterolaemic response to dietary fats, we analysed plasma lipid profiles of CETP-transgenic and control C57BL/6 mice fed standard chow (AIN-93G; AIN), a low-fat diet, and diets high in butter (saturated fatty acids; SFA), high-oleic acid safflower oil (monounsaturated fatty acids; MUFA), and safflower oil (polyunsaturated fatty acids; PUFA) for 5 weeks. Each group contained four or five mice. There were significant diet and dietxgenotype effects on plasma total cholesterol (TC; and respectively), liver TC ( and respectively), and esterified cholesterol (EC; and respectively); diet effects on plasma triacylglycerol liver free cholesterol and body weight a genotype effect on body-weight gain and a dietxgenotype effect on energy intake In transgenic mice the SFA diet caused significantly higher plasma TC than the PUFA diet In control mice MUFA and PUFA diets, but not the SFA diet, caused significantly higher plasma TC than the low-fat and AIN diets Transgenic mice fed PUFA had lower plasma TC while transgenic mice fed MUFA had lower LDL+VLDL-cholesterol than controls in the same dietary groups. Transgenic mice fed MUFA and PUFA diets also had significantly higher liver TC and respectively) and EC and respectively) than controls fed the same diets. In the present study we showed that: (1) CETP transgenic mice had a cholesterolaemic response to dietary fats similar to that in human subjects; (2) CETP transgenic mice fed PUFA showed significantly lower plasma TC, while those fed MUFA had lower LDL+VLDL-cholesterol than controls; (3) hepatic accumulation of cholesterol, possibly resulting from the combination of the enhanced cholesteryl ester transfer to apolipoprotein B-containing lipoproteins and increased hepatic uptake of cholesterol, may contribute to the cholesterol-lowering effect of MUFA and PUFA in CETP-transgenic mice; (4) CETP may play a role in appetite and/or energy regulation.     

Expression of the mouse metallothionein-I and -II genes provides a reproductive advantage during maternal dietary zinc deficiency.

The function of metallothionein in zinc homeostasis was examined by using mice homozygous for knockout (KO) of the metallothionein-I or -II (MT-I and MT-II) genes. Pregnant MT-I/II KO mice or control mice were fed a zinc-deficient (1 microg/g or 5 microg/g) diet or a zinc-adequate (50 microg/g) diet during specific periods of pregnancy, and the effects on morphogenesis of the embryos were determined at day 14 of pregnancy (day 1 = vaginal plug). In the homozygous MT-I/II KO, as well as in the nontransgenic control mice, severe dietary zinc deficiency (1 microg/g) beginning on day 1 of pregnancy was embryotoxic and teratogenic, and the majority of the embryos in both strains were dead by mid-gestation. However, 53% of the surviving embryos in the MT-I/II KO mice were morphologically abnormal compared to only 32% of the embryos in the control mice. In subsequent experiments, moderate dietary zinc deficiency (5 microg/g beginning on day 1 of pregnancy or 1 microg/g dietary zinc beginning on day 8 of pregnancy) exerted teratogenic, but not embryotoxic effects. Embryos in the MT-I/II KO mice were 260 to 290% as likely to develop abnormally than were embryos in the control mice fed these same diets. These results demonstrate that the expression of the MT-I and -II genes in pregnant females improves reproductive success during maternal dietary zinc deficiency.     

蝾螈精子发生及其在生殖毒理学中应用

20多年来 ,科学家们对环境中存在的许多类激素样化学物逐步重视 ,以鱼类、鸟类、海龟、水蛇等为观察对象进行了许多研究 ,但主要偏重于对它们的种群数量的影响和生殖器畸形等调查研究 [1～ 6 ] 。种族的繁衍离不开精子的发生过程 ,因而对化学物的雄性生殖毒性的研究有极其重要的意义。然而至今环境有害物质对雄性生殖细胞的遗传毒性效应的研究很少 ,而重点放在从体细胞的遗传毒性效应外推到生殖细胞。这种外推存在着较大的误差 ,所以有必要发展直接观察有害因素直接对生殖细胞产生遗传毒性效应的检测方法 ,对有害因素的生殖毒性作用过程和机…     

Assessment of the reproductive toxicology of bromochlorodifluoromethane (BCF, halon 1211) in the rat.

The effect of bromochlorodifluoromethane (BCF) on reproduction in the rat has been investigated in two studies. Pregnant female rats were exposed by inhalation to 1000, 10,000, or 50,000 ppm BCF for six hours a day on days six to 15 of gestation (day of mating = day 0). Exposure to 50,000 ppm BCF caused a reduction in maternal weight gain over the exposure period but there was no evidence of either teratogenicity or embryo/fetotoxicity at any concentration. In a study designed to assess the potential effect of BCF during a complete reproductive cycle male and female rats were exposed to 5000 ppm or 25,000 ppm BCF for six hours a day for five days a week for 10 weeks (males) or three weeks (females) before mating. Exposure to BCF continued during mating and up to day 20 of gestation for half the females which were subsequently allowed to litter and the development of their offspring monitored. The remaining females were removed from exposure to BCF after mating and killed on day 20 of gestation for examination of their uterine contents. There were no effects on adult fertility, pup numbers, survival, or pup development. It was concluded that BCF had no reproductive toxicity potential in the rat.     

镉污染对育龄妇女生殖健康的影响

目的 探讨福建省政和县环境镉污染对女性生殖健康的影响。方法 根据环境镉污染检测结果,对镉污染较严重的2个自然村育龄妇女的生殖健康状况作调查,并与非污染区育龄妇女的生殖健康状况作对比。结果 污染区育龄妇女中,未婚女性的月经周期异常率、痛经发生率(分别为19.1％和42.6％)均高于非污染区(分别为5.7％和18.9％);污染区已婚妇女不孕症发生率(6.3％)高于非污染区已婚妇女(1.1％);已婚妇女前两胎妊娠时频发恶心、频发呕吐的发生率,前两胎早产发生率及前两胎死胎死产发生率(分别为44.7％、31.7％、10.27％和4.23％)高于非污染区已婚妇女(分别为26.5％、17.8％、2.85％和1.05％),差异均有统计学意义(P<0.05);累积比数模型分析表明:在控制其他因素的影响后,居住在污染区的育龄妇女,其生殖功能受到损害的可能性更大,其相对危险度是居住在非污染区育龄妇女的2.072倍(95％CI:1.526～2.813)。结论 污染区育龄妇女生殖健康的各个方面已受到不同程度的影响。     

铬及其化合物对雄(男)性生殖毒理学研究进展

铬为动物和人体内必需的微量元素,参与糖、蛋白质、核酸和脂肪的代谢,促进机体生长发育,也促进细胞的增殖和分裂。因此,适当剂量的铬对人体健康有利。但长期过量接触铬化合物对人体产生不良影响。铬及其化合物在许多工业生产中被广泛应用。经常暴露于铬化合物的工作场所有冶金、镀铬、不锈钢     

Multicompartment kinetic models for cadmium: I. Effects of zinc on cadmium retention in male mice

A multicompartmental model was fitted to data on cadmium concentrations in male mice published by K. E. Shank, R. J. Vetter, and P. L. Ziemer (1977, Arch. Environ. Contam. Toxicol.6, 63–68 1977, Environ. Res.13, 209–214. The zinc treatment increased the rate of flow of cadmium from rapidly exchanging compartments to slowly exchanging compartments in blood and liver, and possibly increased the rate of release from the slowly exchanging liver compartment. Most other cadmium distribution processes were slowed by zinc treatment, including blood into liver, kidney, gastrointestinal tract, and pancreas, and back into blood from the liver, kidney, and pancreas. Many other processes were slowed less significantly. The rate of excretion processes was nearly unchanged.