Division of Environmental Biotechnology, Genetics & Molecular Biology (EBGMB), ICMR-National Institute for Research in Environmental Health (NIREH), Bhopal, India.
Division of Environmental Biotechnology, Genetics & Molecular Biology (EBGMB), ICMR-National Institute for Research in Environmental Health (NIREH), Bhopal, India.
Reprod Toxicol. 2024 Oct;129:108675. doi: 10.1016/j.reprotox.2024.108675. Epub 2024 Jul 27.
Prenatal exposure to air pollution is a significant risk factor for the mother and the developing foetus. The accumulation of pollutants in the placenta can cause a self-cascade loop of pro-inflammatory cytokine responses and DNA double-strand breaks. Previous research has shown that airborne particulate matter can damage the epigenome and disturb mitochondrial machinery, ultimately impairing placental function. Mitochondria are essential for preserving cellular homeostasis, energy metabolism, redox equilibrium, and epigenetic reprogramming. As these organelles are subtle targets of environmental exposures, any disruption in the signaling pathways can result in epigenomic instability, which can impact gene expression and mitochondrial function. This, in turn, can lead to changes in DNA methylation, post-translational histone modifications, and aberrant expression of microRNAs in proliferating trophoblast cells. The placenta has two distinct layers, cytotrophoblasts, and syncytiotrophoblasts, each with its mitochondria, which play important roles in preeclampsia, gestational diabetes, and overall health. Foetal nucleic acids enter maternal circulation during placental development because of necrotic, apoptotic, and inflammatory mechanisms. These nucleic acids reflect normal or abnormal ongoing cellular changes during prenatal foetal development. Detecting cell-free DNA in the bloodstream can be a biomarker for predicting negative pregnancy-related outcomes and recognizing abnormalities in foetal growth. Hence, a thorough understanding of how air pollution induces epigenetic variations within the placenta could offer crucial insights into underlying mechanisms and prolonged repercussions on foetal development and susceptibility in later stages of life.
产前暴露于空气污染是母亲和发育中的胎儿的一个重要危险因素。污染物在胎盘内的积累会导致促炎细胞因子反应和 DNA 双链断裂的自我级联循环。先前的研究表明,空气中的颗粒物会破坏表观基因组并扰乱线粒体机制,最终损害胎盘功能。线粒体对于维持细胞内稳态、能量代谢、氧化还原平衡和表观遗传重编程至关重要。由于这些细胞器是环境暴露的微妙靶点,任何信号通路的中断都可能导致表观基因组不稳定,从而影响基因表达和线粒体功能。这反过来又会导致增殖滋养细胞中 DNA 甲基化、翻译后组蛋白修饰和 miRNA 表达的异常。胎盘有两层,即滋养细胞和合体滋养细胞,每层都有自己的线粒体,它们在子痫前期、妊娠期糖尿病和整体健康中发挥重要作用。胎儿核酸由于坏死、凋亡和炎症机制在胎盘发育过程中进入母体循环。这些核酸反映了产前胎儿发育过程中正常或异常的持续细胞变化。检测血液中的游离 DNA 可以作为预测不良妊娠相关结局和识别胎儿生长异常的生物标志物。因此,深入了解空气污染如何在胎盘内引起表观遗传变化,可以为潜在机制提供关键见解,并对胎儿发育和生命后期的易感性产生长期影响。