双酚A暴露对KGN细胞m6A修饰水平的影响

doi:10.6040/j.issn.1671-7554.0.2023.0183

摘要/Abstract

摘要： 目的研究双酚A(BPA)暴露对卵巢颗粒细胞功能表观遗传学的影响。方法将人卵巢颗粒瘤细胞(KGN细胞)暴露于BPA(浓度分别为0、0.02、0.2、2、20 μg/mL)24 h,作为溶剂对照组、0.02 μg/mL BPA组、0.2 μg/mL BPA组、2 μg/mL BPA组、20 μg/mL BPA组,测定mRNA m6A的修饰水平和m6A甲基化调控基因的表达变化;Merip-qPCR法检测抗氧化转录因子(Nrf2)的m6A修饰水平。结果 BPA下调mRNA m6A修饰水平(P<0.001),并改变了m6A甲基化调控基因的表达(P<0.05),2 μg/mL BPA组的超氧化物歧化酶(SOD)表达降低(P<0.05),Nrf2的m6A修饰水平降低(P<0.05)。结论 BPA暴露通过下调Nrf2的m6A修饰导致人卵巢颗粒瘤细胞(KGN细胞)氧化应激增加,颗粒细胞功能损伤,对卵巢颗粒细胞表观遗传学产生影响。

关键词: 双酚A, m6A, 表观遗传学, KGN细胞, 氧化应激

Abstract: Objective To investigate the epigenetic effects of bisphenol A(BPA)exposure on the function of ovarian granulosa cells. Methods Human ovarian granuloma cells(KGN cells)were exposed to BPA(0, 0.02, 0.2, 2, 20 μg/mL)for 24 h, which were defined as vehicle group, 0.02μg/mL BPA group, 0.2 μg/mL BPA group, 2 μg/mL BPA group, and 20 μg/mL BPA group, respectively. The modification level of mRNA m6A and expression of m6A RNA methylation-related genes were measured, and the m6A modification level of antioxidant transcription factor(Nrf2)was detected with Merip-qPCR. Results BPA down-regulated the level of mRNA m6A modification(P<0.001)and changed the expression of m6A methylation-related genes(P<0.05). The expression of superoxide dismutase(SOD)and m6A modification level of Nrf2 decreased in the 2 μg/mL BPA group(both P<0.05). Conclusion BPA exposure can increase oxidative stress and damage the function of KGN cells in human ovarian granulosa tumor by down-regulating the m6A modification of Nrf2, which has an effect on the epigenetics of ovarian granulosa cells.

Key words: Bisphenol A, m6A, Epigenetics, KGN cells, Oxidative stress

中图分类号:

闫丛丛,陈辰,谢倩,王亚楠,张鑫璐,张迎春,武斌. 双酚A暴露对KGN细胞m6A修饰水平的影响[J]. 山东大学学报 (医学版), 2023, 61(8): 17-23.

YAN Congcong, CHEN Chen, XIE Qian, WANG Yanan, ZHANG Xinlu, ZHANG Yingchun, WU Bin. Effects of bisphenol A exposure on m6A modification level of KGN cells[J]. Journal of Shandong University (Health Sciences), 2023, 61(8): 17-23.

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