Journal of Shandong University (Health Sciences) ›› 2023, Vol. 61 ›› Issue (8): 17-23.doi: 10.6040/j.issn.1671-7554.0.2023.0183

• 基础医学 • Previous Articles    

Effects of bisphenol A exposure on m6A modification level of KGN cells

YAN Congcong1, CHEN Chen1, XIE Qian2, WANG Yanan2, ZHANG Xinlu2, ZHANG Yingchun2, WU Bin2   

  1. 1. Weifang Medical University, Weifang 261000, Shandong, China;
    2. Reproductive Medicine Centre, Jinan Central Hospital, Jinan 250013, Shandong, China
  • Published:2023-08-30

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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

CLC Number: 

  • R71
[1] Vandenberg LN, Chahoud I, Heindel JJ, et al. Urinary, circulating, and tissue biomonitoring studies indicate widespread exposure to bisphenol A [J]. Environ Health Perspect, 2010, 118(8): 1055-1070.
[2] Lin ML, Hua R, Ma J, et al. Bisphenol A promotes autophagy in ovarian granulosa cells by inducing AMPK/mTOR/ULK1 signaling pathway [J]. Environ Int, 2021, 147: 106298. doi: 10.1016/j.envint.2020.106298.
[3] Wang XY, Jiang SW, Wang LG, et al. Interfering effects of bisphenol A on in vitro growth of preantral follicles and maturation of oocyes [J]. Clin Chim Acta, 2018, 485: 119-125. doi: 10.1016/j.cca.2018.06.041.
[4] Zhu XQ, Tian GG, Yu BL, et al. Effects of bisphenol A on ovarian follicular development and female germline stem cells [J]. Arch Toxicol, 2018, 92(4): 1581-1591.
[5] Moore-Ambriz TR, Acuña-Hernández DG, Ramos-Robles B, et al. Exposure to bisphenol A in young adult mice does not alter ovulation but does alter the fertilization ability of oocytes [J]. Toxicol Appl Pharmacol, 2015, 289(3): 507-514.
[6] Wang W, Hafner KS, Flaws JA. In utero bisphenol A exposure disrupts germ cell nest breakdown and reduces fertility with age in the mouse [J]. Toxicol Appl Pharmacol, 2014, 276(2): 157-164.
[7] Li XY, Xiong XS, Yi CQ. Epitranscriptome sequencing technologies: decoding RNA modifications [J]. Nat Methods, 2016, 14(1): 23-31.
[8] Meyer KD, Jaffrey SR. Rethinking m6A readers, writers, and erasers [J]. Annu Rev Cell Dev Biol, 2017, 33: 319-342. doi: 10.1146/annurev-cellbio-100616-060758.
[9] Zhu ZM, Huo FC, Pei DS. Function and evolution of RNA N6-methyladenosine modification [J]. Int J Biol Sci, 2020, 16(11): 1929-1940.
[10] Cao ZB, Zhang DD, Wang YQ, et al. Identification and functional annotation of m6A methylation modification in granulosa cells during antral follicle development in pigs [J]. Anim Reprod Sci, 2020, 219: 106510. doi: 10.1016/j.anireprosci.2020.106510.
[11] Fan Y, Zhang CS, Zhu GY. Profiling of RNA N6-methyladenosine methylation during follicle selection in chicken ovary [J]. Poult Sci, 2019, 98(11): 6117-6124.
[12] Cayir A, Barrow TM, Guo LQ, et al. Exposure to environmental toxicants reduces global N6-methyladenosine RNA methylation and alters expression of RNA methylation modulator genes [J]. Environ Res, 2019, 175: 228-234. doi: 10.1016/j.envres.2019.05.011.
[13] Mansur A, Adir M, Yerushalmi G, et al. Does BPA alter steroid hormone synthesis in human granulosa cells in vitro? [J]. Hum Reprod, 2016, 31(7): 1562-1569.
[14] Xuan JJ, Sun WJ, Lin PH, et al. RMBase v2.0: deciphering the map of RNA modifications from epitranscriptome sequencing data [J]. Nucleic Acids Res, 2018, 46(D1): D327-D334.
[15] Zhou Y, Zeng P, Li YH, et al. SRAMP: prediction of mammalian N6-methyladenosine(m6A)sites based on sequence-derived features [J]. Nucleic Acids Res, 2016, 44(10): e91. doi:10.1093/nar/gkw104.
[16] Mansur A, Israel A, Combelles CMH, et al. Bisphenol-A exposure and gene expression in human luteinized membrana granulosa cells in vitro [J]. Hum Reprod, 2017, 32(2): 409-417.
[17] Chianese R, Troisi J, Richards S, et al. Bisphenol A in reproduction: epigenetic effects [J]. Curr Med Chem, 2018, 25(6): 748-770.
[18] Zhang S, Deng WL, Liu QY, et al. Altered m6 A modification is involved in up-regulated expression of FOXO3 in luteinized granulosa cells of non-obese polycystic ovary syndrome patients [J]. J Cell Mol Med, 2020, 24(20): 11874-11882.
[19] Zhao TX, Wang JK, Shen LJ, et al. Increased m6A RNA modification is related to the inhibition of the Nrf2-mediated antioxidant response in di-(2-ethylhexyl)phthalate-induced prepubertal testicular injury [J]. Environ Pollut, 2020, 259: 113911. doi: 10.1016/j.envpol.2020.113911.
[20] Xia CL, Wang J, Wu ZY, et al. METTL3-mediated M6A methylation modification is involved in colistin-induced nephrotoxicity through apoptosis mediated by Keap1/Nrf2 signaling pathway [J]. Toxicology, 2021, 462: 152961. doi: 10.1016/j.tox.2021.152961.
[21] Zhao TX, Wang JK, Wu YH, et al. Increased m6A modification of RNA methylation related to the inhibition of demethylase FTO contributes to MEHP-induced Leydig cell injury [J]. Environ Pollut, 2021, 268(Pt A): 115627. doi: 10.1016/j.envpol.2020.115627.
[22] Park MH, Jeong E, Choudhury M. Mono-(2-ethylhexyl)phthalate regulates cholesterol efflux via microRNAs regulated m6A RNA methylation [J]. Chem Res Toxicol, 2020, 33(2): 461-469.
[23] Lin Z, Hsu PJ, Xing XD, et al. Mettl3-/Mettl14-mediated mRNA N6-methyladenosine modulates murine spermatogenesis [J]. Cell Res, 2017, 27(10): 1216-1230.
[24] Mu HY, Zhang T, Yang Y, et al. METTL3-mediated mRNA N6-methyladenosine is required for oocyte and follicle development in mice [J]. Cell Death Dis, 2021, 12(11): 989. doi: 10.1038/s41419-021-04272-9.
[25] Tang C, Klukovich R, Peng HY, et al. ALKBH5-dependent m6A demethylation controls splicing and stability of long 3'-UTR mRNAs in male germ cells [J]. Proc Natl Acad Sci U S A, 2018, 115(2): E325-E333.
[26] Kasowitz SD, Ma J, Anderson SJ, et al. Nuclear m6A reader YTHDC1 regulates alternative polyadenylation and splicing during mouse oocyte development [J]. PLoS Genet, 2018, 14(5): e1007412. doi: 10.1371/journal.pgen.1007412.
[27] Ivanova I, Much C, di Giacomo M, et al. The RNA m6A reader YTHDF2 is essential for the post-transcriptional regulation of the maternal transcriptome and oocyte competence [J]. Mol Cell, 2017, 67(6): 1059-1067.e4.
[28] Jiang ZX, Wang YN, Li ZY, et al. Correction: the m6A mRNA demethylase FTO in granulosa cells retards FOS-dependent ovarian aging [J]. Cell Death Dis, 2021, 12(12): 1114. doi: 10.1038/s41419-021-04016-9.
[29] Sabuncu T, Vural H, Harma M, et al. Oxidative stress in polycystic ovary syndrome and its contribution to the risk of cardiovascular disease [J]. Clin Biochem, 2001, 34(5): 407-413.
[30] Papalou O, Victor VM, Diamanti-Kandarakis E. Oxidative stress in polycystic ovary syndrome [J]. Curr Pharm Des, 2016, 22(18): 2709-2722.
[31] Wang J, Ishfaq M, Xu L, et al. METTL3/m6A/miRNA-873-5p attenuated oxidative stress and apoptosis in colistin-induced kidney injury by modulating Keap1/Nrf2 pathway [J]. Front Pharmacol, 2019, 10: 517. doi: 10.3389/fphar.2019.00517.
[32] Xia CL, Wang J, Wu ZY, et al. METTL3-mediated M6A methylation modification is involved in colistin-induced nephrotoxicity through apoptosis mediated by Keap1/Nrf2 signaling pathway [J]. Toxicology, 2021, 462: 152961. doi: 10.1016/j.tox.2021.152961.
[33] Zhou SM, Li JZ, Chen HQ, et al. FTO-Nrf2 axis regulates bisphenol F-induced leydig cell toxicity in an m6A-YTHDF2-dependent manner [J]. Environ Pollut, 2023, 325: 121393. doi: 10.1016/j.envpol.2023.121393.
[34] Ding H, Li ZQ, Li X, et al. FTO alleviates CdCl2-induced apoptosis and oxidative stress via the AKT/Nrf2 pathway in bovine granulosa cells [J]. Int J Mol Sci, 2022, 23(9): 4948. doi: 10.3390/ijms23094948.
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