论文部分内容阅读
环境内分泌干扰物(Endocrine Disrupting Chemicals,EDCs)广泛分布于环境中,能够对哺乳动物的生殖系统产生多方面干扰。近年来对于EDCs生殖毒性的研究多集中于激素水平和mRNA水平,但有研究发现EDCs能够在生殖过程中引起表观遗传学变化。在DNA甲基化方面,EDCs能够降低PDE4 D4基因的甲基化水平、升高干细胞因子基因(Kitlg)和妊娠相关性血浆蛋白-A基因(PAPP-A)的甲基化水平、改变磷脂酰肌醇3-激酶(Phosphatidylinositol 3-Kinases,PI3K)通路和雌激素受体(Estrogen Receptor,ER)通路中相关基因的甲基化水平,进而影响原始生殖细胞(Primordial Germ Cells,PGCs)的增殖和原始卵泡的生成和发育;EDCs还能够升高细胞色素P450芳香化酶基因(Cyp19a1a)的甲基化水平,干扰性激素的合成。在组蛋白修饰方面,有研究发现EDCs能降低激素合成急性调节蛋白(steroidogenic acute regulatory protein,StAR)组蛋白的乙酰化水平,影响生殖器官的发育。根据这些研究本文综述了EDCs生殖毒性的表观遗传学机制,期望能为以后的研究提供理论依据。
Endocrine Disrupting Chemicals (EDCs) are widely distributed in the environment and can interfere with many aspects of the mammalian reproductive system. In recent years, researches on reproductive toxicity of EDCs have focused on hormone levels and mRNA levels. However, studies have found that EDCs can cause epigenetic changes in the reproductive process. In DNA methylation, EDCs can reduce the methylation level of PDE4 D4 gene, increase the methylation level of Kitlg gene and pregnancy-associated plasma protein-A gene (PAPP-A), and change the level of phosphatidyl The methylation level of related genes in the pathway of Phosphatidylinositol 3 -kinases (PI3K) and estrogen receptor (ER) leads to the proliferation and proliferation of primitive primordial germ cells (PGCs) The formation and development of primordial follicles; EDCs can also increase the methylation level of cytochrome P450 aromatase gene (Cyp19a1a), interfering with the synthesis of sex hormones. In histone modification, it has been found that EDCs can reduce the acetylation level of histone in steroidogenic acute regulatory protein (StAR) and affect the development of reproductive organs. According to these studies, the epigenetic mechanisms of reproductive toxicity of EDCs are reviewed in this paper. The expectation is to provide a theoretical basis for future research.