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环境相关浓度双酚 A(BPA)对正常人类卵巢体外模型基因表达谱的影响。

Impact of Environmentally Relevant Concentrations of Bisphenol A (BPA) on the Gene Expression Profile in an In Vitro Model of the Normal Human Ovary.

机构信息

Department of Life Sciences, Division of Biosciences, College of Health, Medicine and Life Sciences, Brunel University London, Uxbridge UB8 3PH, UK.

Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (WISDEM), University Hospitals Coventry and Warwickshire NHS Trust, Coventry CV2 2DX, UK.

出版信息

Int J Mol Sci. 2022 May 10;23(10):5334. doi: 10.3390/ijms23105334.

Abstract

Endocrine-disrupting chemicals (EDCs), including the xenoestrogen Bisphenol A (BPA), can interfere with hormonal signalling. Despite increasing reports of adverse health effects associated with exposure to EDCs, there are limited data on the effect of BPA in normal human ovaries. In this paper, we present a detailed analysis of the transcriptomic landscape in normal Human Epithelial Ovarian Cells (HOSEpiC) treated with BPA (10 and 100 nM). Gene expression profiles were determined using high-throughput RNA sequencing, followed by functional analyses using bioinformatics tools. In total, 272 and 454 differentially expressed genes (DEGs) were identified in 10 and 100 nM BPA-treated HOSEpiCs, respectively, compared to untreated controls. Biological pathways included mRNA surveillance pathways, oocyte meiosis, cellular senescence, and transcriptional misregulation in cancer. BPA exposure has a considerable impact on 10 genes: , , , , , , , , , and , which are also associated with progesterone-mediated oocyte maturation pathways. Future studies should further explore the effects of BPA and its metabolites in the ovaries in health and disease, making use of validated in vitro and in vivo models to generate data that will address existing knowledge gaps in basic biology, hazard characterisation, and risk assessment associated with the use of xenoestrogens such as BPA.

摘要

内分泌干扰化学物质(EDCs),包括外源性雌激素双酚 A(BPA),可以干扰激素信号。尽管越来越多的报告表明接触 EDCs 会对健康产生不良影响,但关于 BPA 在正常人类卵巢中的作用的数据有限。在本文中,我们对用 BPA(10 和 100 nM)处理的正常人类上皮性卵巢细胞(HOSEpiC)的转录组景观进行了详细分析。使用高通量 RNA 测序确定基因表达谱,然后使用生物信息学工具进行功能分析。与未处理对照相比,在 10 和 100 nM BPA 处理的 HOSEpiC 中分别鉴定出 272 和 454 个差异表达基因(DEG)。生物学途径包括 mRNA 监测途径、卵母细胞减数分裂、细胞衰老和癌症中的转录失调。BPA 暴露对 10 个基因有显著影响: 、 、 、 、 、 、 、 、 ,它们也与孕激素介导的卵母细胞成熟途径有关。未来的研究应进一步探索 BPA 及其代谢物在健康和疾病中的卵巢中的作用,利用经过验证的体外和体内模型来生成数据,以解决与使用外源性雌激素如 BPA 相关的基础生物学、危害特征和风险评估方面的现有知识空白。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53b1/9141570/c473e1a61bc9/ijms-23-05334-g001.jpg

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