Derghal Adel, Djelloul Mehdi, Trouslard Jérôme, Mounien Lourdes
Aix Marseille University, PPSN Marseille, France.
Aix Marseille University, PPSNMarseille, France; Department of Cell and Molecular Biology, Karolinska InstituteStockholm, Sweden.
Front Neurosci. 2016 Jun 30;10:318. doi: 10.3389/fnins.2016.00318. eCollection 2016.
Endocrine-disrupting chemicals (EDCs) are diverse natural and synthetic chemicals that may alter various mechanisms of the endocrine system and produce adverse developmental, reproductive, metabolic, and neurological effects in both humans and wildlife. Research on EDCs has revealed that they use a variety of both nuclear receptor-mediated and non-receptor-mediated mechanisms to modulate different components of the endocrine system. The molecular mechanisms underlying the effects of EDCs are still under investigation. Interestingly, some of the effects of EDCs have been observed to pass on to subsequent unexposed generations, which can be explained by the gametic transmission of deregulated epigenetic marks. Epigenetics is the study of heritable changes in gene expression that occur without a change in the DNA sequence. Epigenetic mechanisms, including histone modifications, DNA methylation, and specific micro-RNAs (miRNAs) expression, have been proposed to mediate transgenerational transmission and can be triggered by environmental factors. MiRNAs are short non-coding RNA molecules that post-transcriptionally repress the expression of genes by binding to 3'-untranslated regions of the target mRNAs. Given that there is mounting evidence that miRNAs are regulated by hormones, then clearly it is important to investigate the potential for environmental EDCs to deregulate miRNA expression and action.
内分泌干扰化学物质(EDCs)是多种天然和合成化学物质,它们可能改变内分泌系统的各种机制,并在人类和野生动物中产生不良的发育、生殖、代谢和神经学影响。对EDCs的研究表明,它们利用多种核受体介导和非受体介导的机制来调节内分泌系统的不同组成部分。EDCs作用的分子机制仍在研究中。有趣的是,已观察到EDCs的一些影响会传递给随后未接触过这些物质的后代,这可以通过失调的表观遗传标记的配子传递来解释。表观遗传学是研究在DNA序列不变的情况下发生的基因表达的可遗传变化。表观遗传机制,包括组蛋白修饰、DNA甲基化和特定微小RNA(miRNA)的表达,已被提出介导跨代传递,并且可由环境因素触发。miRNA是短的非编码RNA分子,通过与靶mRNA的3'非翻译区结合在转录后抑制基因表达。鉴于越来越多的证据表明miRNA受激素调节,显然研究环境EDCs使miRNA表达和作用失调的可能性很重要。