Mohammed Aamer, Atkin Stephen L, Brennan Edwina
School of Medicine, Royal College of Surgeons in Ireland Bahrain, Adliya 15503, Bahrain.
School of Postgraduate Studies & Research, Royal College of Surgeons in Ireland Bahrain, Adliya 15503, Bahrain.
J Xenobiot. 2025 May 12;15(3):72. doi: 10.3390/jox15030072.
Phthalates, a group of synthetic non-persistent organic chemicals commonly used as solvents and plasticisers, have been associated with a range of detrimental health effects. These endocrine disrupting chemicals (ECDs) may exert their effects through epigenetic changes such as altered microRNA (miRNA) expression. miRNAs are short non-coding endogenous RNA transcripts that are preferentially expressed in various tissues and cell types and can circulate in body fluids, thereby regulating gene expression and acting as mediators for intercellular communication. As miRNAs mostly target protein-coding transcripts, they are involved in nearly all networks that regulate developmental and pathological processes. In this review, we provide an overview of human, in vivo and in vitro studies assessing altered miRNA expression due to phthalate exposure and their biological effects. Importantly, this study suggests that the mechanism of phthalate action may in part be mediated by epigenetic changes, affecting a large number of different proteins. This is indicative that alterations in miRNA expression induced by phthalate exposure are then implicated in a wide range of health conditions, including reproductive dysfunction, oncogenesis, metabolic disorders, and neurodevelopmental outcomes. Exposure to phthalates and their metabolites predominantly results in the upregulation of miRNAs. Dysregulation of miR-34a, miR-15b, miR-141, miR-184, miR-19a, miR-125, and miR-let-7 were observed across several studies. More research involving human participants combined with mechanistic studies integrating mRNA target analysis would be beneficial in understanding the downstream effects of phthalate exposure on gene expression and grasping the broader biological implications.
邻苯二甲酸盐是一类常用作溶剂和增塑剂的合成非持久性有机化学品,与一系列有害健康影响相关。这些内分泌干扰化学物质(ECDs)可能通过表观遗传变化发挥作用,如改变微小RNA(miRNA)表达。miRNAs是短的非编码内源性RNA转录本,在各种组织和细胞类型中优先表达,并可在体液中循环,从而调节基因表达并充当细胞间通讯的介质。由于miRNAs大多靶向蛋白质编码转录本,它们几乎参与了所有调节发育和病理过程的网络。在本综述中,我们概述了评估因邻苯二甲酸盐暴露导致的miRNA表达改变及其生物学效应的人体、体内和体外研究。重要的是,本研究表明邻苯二甲酸盐的作用机制可能部分由表观遗传变化介导,影响大量不同蛋白质。这表明邻苯二甲酸盐暴露诱导的miRNA表达改变与广泛的健康状况有关,包括生殖功能障碍、肿瘤发生、代谢紊乱和神经发育结果。接触邻苯二甲酸盐及其代谢物主要导致miRNAs上调。在多项研究中观察到miR-34a、miR-15b、miR-141、miR-184、miR-19a、miR-125和miR-let-7的失调。更多涉及人类参与者的研究以及整合mRNA靶标分析的机制研究,将有助于理解邻苯二甲酸盐暴露对基因表达的下游影响,并把握更广泛的生物学意义。