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对双甲的暴露会影响卵巢颗粒细胞中转录组范围内的N6-甲基氨酸甲基化

Yuxia Zhang¹, Congcong Yan¹, Qian Xie¹

¹Department of Reproductive Medicine, Central Hospital Affiliated to Shandong First Medical University, Jinan, China.

Ecotoxicology and environmental safety

|February 14, 2024

概括

双甲 (BPA) 暴露会改变女性卵巢细胞中的RNA甲基化,影响生殖健康. 这项研究确定了特定的基因和lncRNAs作为BPA诱导的生殖毒性的潜在生物标志物.

科学领域:

生殖毒理学生殖毒理学
表观遗传学在表观遗传学中,表观遗传学是指表观遗传学.
分子生物学分子生物学

背景情况:

双A (BPA) 是一种内分泌干扰物,与生殖毒性有关.
环境BPA暴露可以改变转录组表观遗传修饰.
BPA对女性生殖过程中的m6A甲基化作用的确切机制尚不清楚.

研究的目的:

调查BPA暴露会改变女性卵巢颗粒细胞中的信使RNA (mRNA) N6-甲基氨酸 (m6A) 修饰水平的假设.
为了确定受BPA暴露影响的特定转录和调节基因.
探索BPA诱导的生殖系统损伤的潜在生物标志物.

主要方法:

颗粒细胞暴露于BPA24小时.
评估了RNA甲基化调节剂 (METTL3,METTL14,ALKBH5,FTO) 的表达和全球m6A水平.
用甲基化RNA免疫沉测序 (MERIP-seq) 分析了全基因组的m6A修饰变化.
对差异甲基化转录进行了基因本体学 (GO) 和通路分析.
使用RT-qPCR和IGV软件对所选基因 (IMPA1,MCOLN1,DCTN3,BRCA2,MALAT1,XIST) 进行验证.

主要成果:

暴露于BPA显著改变了RNA甲基化调节基因表达和全球m6A水平.
MERIP-seq确定了1595个差异甲基化mRNA转录和50个差异甲基化长非编码RNA (lncRNA) 转录.
分析揭示了不同组的高/低甲基和上/下调的基因.
受影响的基因主要丰富于与脂质代谢,细胞增殖和亡相关的途径.
鉴定出 lncRNAs MALAT1 和 XIST 是潜在的新生物标志物.

结论:

暴露于BPA会诱导女性卵巢颗粒细胞表体转录组的显著变化.
这些RNA甲基化变化与关键细胞过程中发生的干扰有关.
马拉特1和XIST lncRNAs显示为BPA干扰女性生殖健康的生物标志物具有前途.

关键词:

双甲 (BPA) 是一种副转录ome 副转录ome 副转录ome 副转录ome 女性的生殖系统是女性的生殖系统.在 LncRNAs 中.在M6A-seqq.基因组甲基化修饰RNA的修饰.

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