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对羟基苯甲酸酯暴露会改变自发永生化的分泌型小鼠输卵管上皮(MOE)细胞的细胞周期进程和存活率。

Paraben exposure alters cell cycle progression and survival of spontaneously immortalized secretory murine oviductal epithelial (MOE) cells.

作者信息

Ziv-Gal Ayelet, Berg Malia D, Dean Matthew

机构信息

Department of Comparative Biosciences, University of Illinois at Urbana-Champaign, Urbana, IL, USA.

Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, USA.

出版信息

Reprod Toxicol. 2021 Mar;100:7-16. doi: 10.1016/j.reprotox.2020.12.016. Epub 2020 Dec 24.

Abstract

The mammalian oviduct is a central organ for female reproduction as it is the site of fertilization and it actively transports the embryo to the uterus. The oviduct is responsive to ovarian steroids and thus, it is a potential target of endocrine disrupting chemicals. Parabens are antimicrobial compounds that are prevalently found in daily-used products. However, recent studies suggest that some parabens can impact female reproductive health. Yet, their effects on the oviduct are unknown. Here, we hypothesized that in vitro exposure of immortalized murine oviductal secretory epithelial (MOE) cells to methylparaben or propylparaben will result in disrupted cell cycle progression and increased cell death by dysregulation of molecular mechanisms that involve the cell cycle and apoptosis. Thus, we examined the effects of exposure to parabens on cell proliferation, cell cycle progression by flow cytometry, and mRNA levels of major cell cycle regulators and apoptotic factors, in MOE cells. Protein levels of estrogen and progesterone receptors were also quantified. Differences between treatments and controls were analyzed by linear mixed model followed by Dunnett post-hoc tests. The results indicate that methylparaben and propylparaben selectively reduce MOE cellular proliferation and colony numbers, compared to controls. Additionally, paraben exposure selectively dysregulates the progression through the cell cycle and decreases the levels of cell cycle regulators, compared to controls. Last, paraben selectively alters the levels of progesterone receptor. Overall, these findings suggest that parabens can affect mouse oviductal secretory epithelial cell proliferation and survival.

摘要

哺乳动物的输卵管是雌性生殖的核心器官,因为它是受精的场所,并能将胚胎主动输送到子宫。输卵管对卵巢类固醇有反应,因此它是内分泌干扰化学物质的潜在靶点。对羟基苯甲酸酯是一种抗菌化合物,普遍存在于日常用品中。然而,最近的研究表明,某些对羟基苯甲酸酯会影响女性生殖健康。然而,它们对输卵管的影响尚不清楚。在此,我们假设将永生化的小鼠输卵管分泌上皮(MOE)细胞在体外暴露于甲基对羟基苯甲酸酯或丙基对羟基苯甲酸酯会导致细胞周期进程紊乱,并通过涉及细胞周期和凋亡的分子机制失调而增加细胞死亡。因此,我们研究了对羟基苯甲酸酯暴露对MOE细胞的细胞增殖、通过流式细胞术检测的细胞周期进程以及主要细胞周期调节因子和凋亡因子的mRNA水平的影响。还对雌激素和孕激素受体的蛋白水平进行了定量分析。通过线性混合模型分析处理组和对照组之间的差异,随后进行Dunnett事后检验。结果表明,与对照组相比,甲基对羟基苯甲酸酯和丙基对羟基苯甲酸酯选择性地降低了MOE细胞的增殖和集落数量。此外,与对照组相比,对羟基苯甲酸酯暴露选择性地使细胞周期进程失调,并降低了细胞周期调节因子的水平。最后,对羟基苯甲酸酯选择性地改变了孕激素受体的水平。总体而言,这些发现表明对羟基苯甲酸酯会影响小鼠输卵管分泌上皮细胞的增殖和存活。

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