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对羟基苯甲酸丙酯抑制小鼠腔前卵泡生长,改变甾体生成,并上调细胞周期和凋亡调节剂的水平。

Propylparaben inhibits mouse cultured antral follicle growth, alters steroidogenesis, and upregulates levels of cell-cycle and apoptosis regulators.

机构信息

Department of Veterinary Clinical Medicine, University of Illinois, Urbana, IL, USA.

School of Veterinary Science, Massey University, Palmerston North, New Zealand.

出版信息

Reprod Toxicol. 2019 Oct;89:100-106. doi: 10.1016/j.reprotox.2019.07.009. Epub 2019 Jul 12.

Abstract

Propylparaben is prevalently used in cosmetics, pharmaceuticals, and foods; yet, its direct effects on the mammalian ovary are unknown. We investigated the direct effects of propylparaben on the growth and steroidogenic function of mouse antral follicles. Antral follicles were isolated from the ovaries of Swiss mice (age: 32-42 days) and cultured in media with dimethylsulfoxide vehicle control or propylparaben (0.01-100 μg/mL) for 24-72 h. Follicle diameter was measured every 24 h to assess growth. Follicles and media were collected at 24 and 72 h for gene expression and hormone measurements. Propylparaben (100 μg/mL) significantly inhibited follicle growth (48-72 h). Further, propylparaben exposure increased expression of cell cycle regulators (Cdk4, Cdkn1a), an apoptotic factor (Bax), and a key steroidogenic regulator (Star). In media, propylparaben decreased accumulation of dehydroepiandrosterone-sulfate, but increased testosterone and 17β-estradiol. Overall, our findings suggest that propylparaben disrupts antral follicle growth and steroidogenic function by altering the cell-cycle, apoptosis, and steroidogenesis pathways.

摘要

丙基对羟基苯甲酸酯广泛应用于化妆品、药品和食品中,但它对哺乳动物卵巢的直接影响尚不清楚。我们研究了丙基对羟基苯甲酸酯对小鼠腔前卵泡生长和类固醇生成功能的直接影响。从小鼠(年龄:32-42 天)卵巢中分离腔前卵泡,并在含有二甲亚砜载体对照或丙基对羟基苯甲酸酯(0.01-100μg/ml)的培养基中培养 24-72 小时。每隔 24 小时测量卵泡直径以评估生长情况。在 24 和 72 小时收集卵泡和培养基进行基因表达和激素测量。丙基对羟基苯甲酸酯(100μg/ml)显著抑制卵泡生长(48-72 小时)。此外,丙基对羟基苯甲酸酯暴露增加了细胞周期调节剂(Cdk4、Cdkn1a)、凋亡因子(Bax)和关键类固醇生成调节剂(Star)的表达。在培养基中,丙基对羟基苯甲酸酯减少了脱氢表雄酮硫酸盐的积累,但增加了睾酮和 17β-雌二醇。总之,我们的研究结果表明,丙基对羟基苯甲酸酯通过改变细胞周期、凋亡和类固醇生成途径破坏腔前卵泡的生长和类固醇生成功能。

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