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个体和联合暴露于 BPA、BPF、BPS 对小鼠精母细胞 GC-2 细胞系的细胞、转录组和甲基组的影响。

Cellular, transcriptomic and methylome effects of individual and combined exposure to BPA, BPF, BPS on mouse spermatocyte GC-2 cell line.

机构信息

Department of Reproduction and Gynecological Endocrinology, Medical University of Bialystok, M. Sklodowskiej- Curie 24a, 15-276 Bialystok, Poland.

Department of Biology and Pathology of Human Reproduction, Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Olsztyn, Marii Sklodowskiej-Curie 24a, 15-276 Bialystok, Poland.

出版信息

Toxicol Appl Pharmacol. 2018 Nov 15;359:1-11. doi: 10.1016/j.taap.2018.09.006. Epub 2018 Sep 6.

DOI:10.1016/j.taap.2018.09.006
PMID:30196065
Abstract

Environmental factors, particularly xenoestrogens adversely affect reproductive health and their main mechanism is based on steroid-signaling pathway alterations. The presence of bisphenol A (BPA) in the environment has been confirmed and it is about to be replaced by analogues such as bisphenol F (BPF) and bisphenol S (BPS). Whether the BPF and BPS exert similar adverse effects to BPA has become the subject of intense scientific scrutiny. The aim of the present study was to evaluate and compare the cellular, transcriptomic and methylome effects of exposure to BPA, BPF, BPS individually and in combination on GC-2 spermatocyte cell line. The results show that all studied compounds affect cell viability, induce apoptosis and cause cellular damage. BPA, BPF and BPS also influence GC-2 cell steroid receptor and steroidogenesis related genes expressions. In addition to specific molecular mechanisms, all studied compounds also increase global DNA methylation. Exposure to a combination of all the studied compounds caused comparable effects on cell culture to each of them examined separately. These data suggest that exposure to BPA and its main substitutes- BPF and BPS induced multitude of effects and hence, BPF and BPS are not safe alternative to BPA in terms of male reproductive health.

摘要

环境因素,特别是外源性雌激素,会对生殖健康产生不利影响,其主要机制是基于甾体信号通路的改变。环境中双酚 A(BPA)的存在已得到证实,它即将被类似物如双酚 F(BPF)和双酚 S(BPS)所取代。BPF 和 BPS 是否会产生与 BPA 相似的不良影响,已成为科学研究的热点。本研究旨在评估和比较 BPA、BPF、BPS 单独及联合暴露对 GC-2 精母细胞系的细胞、转录组和甲基组的影响。结果表明,所有研究的化合物都影响细胞活力,诱导细胞凋亡,并导致细胞损伤。BPA、BPF 和 BPS 还影响 GC-2 细胞甾体受体和甾体生成相关基因的表达。除了特定的分子机制外,所有研究的化合物还会增加全基因组 DNA 甲基化。所有研究化合物的组合暴露对细胞培养的影响与它们各自单独暴露的影响相当。这些数据表明,BPA 及其主要替代品 BPF 和 BPS 的暴露会引起多种影响,因此,就男性生殖健康而言,BPF 和 BPS 并不是 BPA 的安全替代品。

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