Franczak Anita, Drzewiecka Ewa Monika, Kozlowska Wiktoria, Zmijewska Agata, Wydorski Pawel Jozef
Department of Animal Anatomy and Physiology, Faculty of Biology and Biotechnology, University of Warmia and Mazury in Olsztyn, Oczapowskiego 1A, 10- 719, Olsztyn, Poland.
Department of Animal Anatomy and Physiology, Faculty of Biology and Biotechnology, University of Warmia and Mazury in Olsztyn, Oczapowskiego 1A, 10- 719, Olsztyn, Poland.
Theriogenology. 2023 Apr 1;200:136-146. doi: 10.1016/j.theriogenology.2023.02.005. Epub 2023 Feb 7.
Previous research by the authors indicated that an extremely low-frequency electromagnetic field (ELF-EMF) evokes molecular alterations in the porcine myometrium. It was hypothesized that the ELF-EMF could induce alterations in the epigenetic regulation of gene expression in the myometrium. In the current study, slices of the porcine myometrium during the peri-implantation period (n = 4) were used for further in vitro exposition to ELF-EMF (50 Hz, 8 mT, 2 h treatment duration). The study tested whether the ELF-EMF may affect: 1/the expression of DNA (cytosine-5)-methyltransferase 1 (DNMT1) and DNA (cytosine-5)-methyltransferase 3a (DNMT3a), 2/the level of genomic DNA methylation, and 3/the level of amplification of methylated and unmethylated variants of promoter regions of selected genes with altered expression in response to ELF-EMF. It was found that ELF-EMF treatment increased DNMT1, decreased DNMT3a mRNA transcript and protein abundance, and increased the level of genomic DNA methylation. The direction of alterations in the level of amplification of methylated and unmethylated variants of the promoter region of selected genes with altered expression, i.e. prodynorphin (PDYN), interleukin 15 (IL15) signal transducer and activator of transcription 5A (STAT5A), tumor necrosis factor (TNF), and between down-regulated genes were early growth response 2 (EGR2), hyaluronan and proteoglycan link protein 1 (HAPLN1), and uteroferrin associated basic protein-2 (UABP2), mostly involving the direction of changes in their transcriptional activity, which was evaluated in a previous study by the authors. Thus, ELF-EMF radiation disturbs epigenetic mechanisms, which may underlay ELF-EMF-related transcriptomic alterations in the myometrium.
作者之前的研究表明,极低频电磁场(ELF-EMF)可引起猪子宫肌层的分子变化。据推测,ELF-EMF可能会诱导子宫肌层基因表达的表观遗传调控发生改变。在本研究中,使用植入前期猪子宫肌层切片(n = 4)进行进一步的体外ELF-EMF暴露(50 Hz,8 mT,处理持续时间2小时)。该研究测试了ELF-EMF是否可能影响:1/DNA(胞嘧啶-5)-甲基转移酶1(DNMT1)和DNA(胞嘧啶-5)-甲基转移酶3a(DNMT3a)的表达;2/基因组DNA甲基化水平;3/在响应ELF-EMF时表达发生改变的选定基因启动子区域甲基化和未甲基化变体的扩增水平。结果发现,ELF-EMF处理增加了DNMT1,降低了DNMT3a mRNA转录本和蛋白质丰度,并提高了基因组DNA甲基化水平。在表达发生改变的选定基因启动子区域甲基化和未甲基化变体的扩增水平变化方向上,即前强啡肽(PDYN)、白细胞介素15(IL15)信号转导和转录激活因子5A(STAT5A)、肿瘤坏死因子(TNF),以及下调基因之间的早期生长反应2(EGR2)、透明质酸和蛋白聚糖连接蛋白1(HAPLN1)和子宫铁蛋白相关碱性蛋白-2(UABP2),大多涉及它们转录活性的变化方向,这是作者在之前的一项研究中评估的。因此,ELF-EMF辐射扰乱了表观遗传机制,这可能是子宫肌层中与ELF-EMF相关的转录组改变的基础。