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内分泌干扰物呋喃对 Sprague Dawley 大鼠生殖生理学的影响:F1 代扩展一代生殖毒性研究(EOGRTS)。

Effects of endocrine disruptor furan on reproductive physiology of Sprague Dawley rats: An F1 Extended One-Generation Reproductive Toxicity Study (EOGRTS).

机构信息

Reproductive Physiology Laboratory, Faculty of Biological Sciences, Department of Animal Sciences, Quaid-i-Azam University, Islamabad, Pakistan.

Division of Physiology, Department of Neuroscience, Uppsala Biomedical Centre (BMC), Uppsala University, Uppsala, Sweden.

出版信息

Hum Exp Toxicol. 2020 Aug;39(8):1079-1094. doi: 10.1177/0960327120911416. Epub 2020 Mar 16.

DOI:10.1177/0960327120911416
PMID:32174189
Abstract

The present study investigated the reproductive toxicity of furan in an Extended One-Generation Reproductive Toxicity Study in rats. Sprague Dawley F0 weaning rats (30 per sex per group) were exposed to furan orally at 0, 1, 2.5, 5, and 10 mg kg for 10 weeks (males) and 2 weeks (females) and then mated. Results of F0 indicated that in the furan-treated groups (5 mg kg and 10 mg kg), body weight (bw) gain decreased during prebreed and gestational period while increased during lactation periods. F0 animals prebreeding exposure resulted in head tilt and foot splay at 10 mg kg. Number of live pups at birth were decreased ( < 0.001) at 10 mg kg. At postnatal day (PND) 70, a significant ( = 0.03) decrease in testosterone levels of male rats and estrogen levels of female rats ( = 0.05) was observed in 10 mg kg furan-treated group in F1 generation. Luteinizing hormone, follicle-stimulating hormone, and progesterone levels were also reduced, but their reduction was not statistically significant in all groups. In higher dose furan group (10 mg kg), testicular and ovarian weights were reduced in F1 generation at PND 70, with decreased daily sperm production ( = 0.01) and disturbed estrous cyclicity ( < 0.01). Some histopathological changes were also observed in testis and ovaries in groups whose parents were previously exposed to 10 mg kg bw of furan group. Based on the above results, it is suggested that exposure to food-based contaminant furan induced remarkable changes in the F0 (parental stage) and F1 (offspring, pubertal, and adult stage) generations of Sprague Dawley rats.

摘要

本研究在大鼠扩展一代生殖毒性研究中调查了呋喃的生殖毒性。30 只 Sprague Dawley F0 断奶大鼠(每组雌雄各 30 只)经口暴露于 0、1、2.5、5 和 10mg/kg 的呋喃,暴露时间为 10 周(雄性)和 2 周(雌性),然后交配。F0 结果表明,在呋喃处理组(5mg/kg 和 10mg/kg)中,在预配种和妊娠期期间体重(BW)增加减少,而在哺乳期期间增加。F0 动物预配种暴露导致 10mg/kg 组出现头部倾斜和足部张开。10mg/kg 组出生时活产仔数减少(<0.001)。在 F1 代中,在 10mg/kg 呋喃处理组中,雄性大鼠的睾酮水平和雌性大鼠的雌激素水平(=0.05)在产后第 70 天显著(=0.03)降低。促黄体生成素、促卵泡激素和孕酮水平也降低,但在所有组中降低均不显著。在较高剂量呋喃组(10mg/kg)中,在 F1 代中,在产后第 70 天,睾丸和卵巢重量降低,每日精子产量减少(=0.01),发情周期紊乱(<0.01)。在先前暴露于 10mg/kg BW 呋喃的组中,还观察到睾丸和卵巢的一些组织病理学变化。基于上述结果,建议接触基于食物的污染物呋喃会导致 Sprague Dawley 大鼠的 F0(亲代阶段)和 F1(后代、青春期和成年阶段)代发生明显变化。

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