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慢性低剂量壬基酚或邻苯二甲酸二(2-乙基己基)酯在小鼠子宫中具有不同的雌激素样反应。

Chronic Low-Dose Nonylphenol or Di-(2-ethylhexyl) Phthalate has a Different Estrogen-like Response in Mouse Uterus.

作者信息

Kim Juhye, Cha Sunyeong, Lee Min Young, Hwang Yeon Jeong, Yang Eunhyeok, Ryou Chongsuk, Jung Hyo-Il, Cheon Yong-Pil

机构信息

Division of Developmental Biology and Physiology, School of Bioscience and Chemistry, Institute for Basic Sciences, Sungshin University, Seoul 02844, Korea.

Dept. of Pharmacy, College of Pharmacy, Hanyang University, Ansan 15588, Korea.

出版信息

Dev Reprod. 2018 Dec;22(4):379-391. doi: 10.12717/DR.2018.22.4.379. Epub 2018 Dec 31.

Abstract

Through the development of organic synthetic skill, chemicals that mimic signaling mediators such as steroid hormones have been exposed to the environment. Recently, it has become apparent that this circumstance should be further studied in the field of physiology. Estrogenic action of chronic low-dose nonylphenol (NP) and di-(2-ethylhexyl) phthalate (DEHP) in mouse uterus was assessed in this study. Ten to twelve-week-old female mice (CD-1) were fed drinking water containing NP (50 or 500 μg/L) or DEHP (133 or 1,330 μg/L) for 10 weeks. Uterine diameter, the thickness of myometrium and endometrium, and the height of luminal epithelial cells were measured and the number of glands were counted. The expression levels of the known 17β-estradiol (E)-regulated genes were evaluated with real-time RT-PCR methodology. The ration of uterine weight to body weight increased in 133 μg/L DEHP. Endometrial and myometrial thickness increased in 133 and 1,330 μg/L DEHP treated groups, and in 50, 500 μg/L NP and 133 μg/L DEHP, respectively. The height of luminal epithelial cell decreased in NP groups. The numbers of luminal epithelial gland were decreased in NP groups but increased in 50 μg/L DEHP group. The histological characters of glands were not different between groups. The mRNA expression profiles of the known 17β-estradiol (E) downstream genes, , were also different between NP and DEHP groups. The expression levels dramatically increased in some genes by the NP or DEHP. Based on these results, it is suggested that the chronic low-dose NP or DEHP works as estrogen-like messengers in uterus with their own specific gene expression-regulation patterns.

摘要

随着有机合成技术的发展,诸如类固醇激素等模拟信号介质的化学物质已进入环境。最近,很明显这种情况在生理学领域应得到进一步研究。本研究评估了慢性低剂量壬基酚(NP)和邻苯二甲酸二(2-乙基己基)酯(DEHP)对小鼠子宫的雌激素作用。将10至12周龄的雌性小鼠(CD-1)用含NP(50或500μg/L)或DEHP(133或1330μg/L)的饮用水喂养10周。测量子宫直径、肌层和子宫内膜厚度以及腔上皮细胞高度,并计数腺体数量。用实时RT-PCR方法评估已知的17β-雌二醇(E)调节基因的表达水平。133μg/L DEHP组子宫重量与体重之比增加。133和1330μg/L DEHP处理组以及50、500μg/L NP和133μg/L DEHP组的子宫内膜和肌层厚度分别增加。NP组腔上皮细胞高度降低。NP组腔上皮腺体数量减少,但50μg/L DEHP组增加。各组之间腺体的组织学特征没有差异。NP组和DEHP组之间已知的17β-雌二醇(E)下游基因的mRNA表达谱也不同。某些基因的表达水平因NP或DEHP而显著增加。基于这些结果,表明慢性低剂量NP或DEHP在子宫中作为雌激素样信使起作用,具有其自身特定的基因表达调控模式。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b13/6344359/9bdbeab77d3c/dr-22-4-379-g1.jpg

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