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Spermatotoxicity and Transgenerational Effects of Dioxin

二恶英的精子毒性和跨代效应

基本信息

批准号：
12836006
负责人：
NAKAJIMA Hiroo
金额：
$ 2.3万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12836006/
关键词：
Dioxins Mouse Reproductive toxicity Teratogenicity Transgenerational effects Environmental Contamination Genetic Effects

项目摘要

We examined the morphological, functional and molecular abnormalities in the offspring of mice (B6C3F_1 and CB.17F_1) exposed to dioxins.A single i.p. or p.o. administration of 100 or 50 ng of 2, 3, 7, 8-Tetrachlorodibenzo-p-dioxin per g of body weight was given to male mice, and mated with untreated female mice to examine the morphological and functional abnormalities in their offspring. On Day 18 of gestation, their fetuses and fetal appendages were removed by the cesarian operation. Implants, early deaths, late deaths, and the external abnormality of living fetuses were examined, and fetuses were resuscitated by pudding with tissue paper to check RDS (respiratory distress syndrome).Up to now, we have gotten following results ; the incidence of implantation decreased significantly in the dioxin (100ng/g) treated group in contrast to control group. And significant increase of morphological anormalies (p<0.05) was observed in CB.17F_1 mice, but in B6C3F_1, an increase was marginal significant (p=0.055). The malformations observed in the dioxin treated group were dwarf, omphalocele, agnathy, cleft palate, kinky tail, short tail, agenesis of the testis, general edema, syndacryly, and in the control group were dwarf, Meckel diverticulum, open eye, and cleft palate.Additionally, dose dependency (increasing incidence of early deaths, malformation and decrease of implantation, living fetus) was also observed in B6C3F_1 mice.Furthermore, significant increase of functional defects like respiratory distress syndrome was observed in the F_1 fetuses of TCDD treated male mice of two different strains.Increased incidence of molecular changes, i. e., length polymorphism of repetitive DNA sequences (pc-3) was detected but it was not yet significant at present. Large scale experiments are in progress.

我们研究了暴露于二恶英的小鼠后代（B6C3F_1和CB. 17F_1）的形态、功能和分子异常。对雄性小鼠给予每克体重100或50 ng的2，3，7，8-四氯二苯并-对-二恶英，并与未处理的雌性小鼠交配，以检查其后代的形态和功能异常。在妊娠第18天，通过剖腹手术切除其胎儿和胎儿附件。结果表明，二恶英（100 ng/g）处理组的着床率明显低于对照组，但死亡率明显低于对照组。CB.17F_1小鼠的形态异常明显增加（p<0.05），而B6 C3 F_1小鼠的形态异常增加幅度较小（p=0.055）。在二恶英处理组中观察到的畸形是侏儒、脐膨出、无颌、腭裂、扭尾、短尾、睾丸发育不全、全身水肿、并泪，而在对照组中观察到的畸形是侏儒、美克尔憩室、睁眼和腭裂。在B6C3F_1小鼠中也观察到（早期死亡、畸形和着床、活胎减少的发生率增加）。TCDD处理的两种不同品系雄性小鼠F_1胎仔中呼吸窘迫综合征等功能缺陷的发生率均显著增加。例如，检测到重复DNA序列（pc-3）的长度多态性，但目前尚不显著。大规模的实验正在进行中。