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Paraben exposure alters cell cycle progression and survival of spontaneously immortalized secretory murine oviductal epithelial (MOE) cells
Reproductive Toxicology ( IF 3.3 ) Pub Date : 2020-12-24 , DOI: 10.1016/j.reprotox.2020.12.016
Ayelet Ziv-Gal 1 , Malia D Berg 2 , Matthew Dean 2
Affiliation  

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.



中文翻译:

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

哺乳动物的输卵管是雌性生殖的中心器官,因为它是受精的部位,它积极地将胚胎输送到子宫。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目标。对羟基苯甲酸酯是普遍存在于日常使用的产品中的抗菌化合物。然而,最近的研究表明,一些对羟基苯甲酸酯会影响女性的生殖健康。然而,它们对输卵管的影响尚不清楚。在这里,我们假设在体外将永生化鼠输卵管分泌上皮 (MOE) 细胞暴露于对羟基苯甲酸甲酯或对羟基苯甲酸丙酯会导致细胞周期进程中断和细胞死亡增加,这是由于涉及细胞周期和细胞凋亡的分子机制失调。因此,我们通过流式细胞术检查了暴露于对羟基苯甲酸酯对细胞增殖、细胞周期进程以及 MOE 细胞中主要细胞周期调节剂和凋亡因子的 mRNA 水平的影响。雌激素和孕激素受体的蛋白质水平也被量化。通过线性混合模型和 Dunnett 事后检验分析处理和对照之间的差异。结果表明,与对照相比,对羟基苯甲酸甲酯和对羟基苯甲酸丙酯选择性地减少了MOE细胞增殖和集落数。此外,与对照组相比,对羟基苯甲酸酯暴露选择性地失调整个细胞周期的进程并降低细胞周期调节剂的水平。最后,对羟基苯甲酸酯选择性地改变孕酮受体的水平。总的来说,这些发现表明对羟基苯甲酸酯可以影响小鼠输卵管分泌上皮细胞的增殖和存活。

更新日期:2020-12-26
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