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人类妊娠中的线粒体毒性:过去10年临床及实验方法的最新进展

Mitochondrial toxicity in human pregnancy: an update on clinical and experimental approaches in the last 10 years.

作者信息

Morén Constanza, Hernández Sandra, Guitart-Mampel Mariona, Garrabou Glòria

机构信息

Muscle Research and Mitochondrial Function Laboratory, Cellex-IDIBAPS-Faculty of Medicine-University of Barcelona, Internal Medicine Service-Hospital Clínic of Barcelona, Barcelona 08036, Spain.

Centro de Investigación Biomédica en Red (CIBER) de Enfermedades Raras, CIBERER, Valencia 46010, Spain.

出版信息

Int J Environ Res Public Health. 2014 Sep 22;11(9):9897-918. doi: 10.3390/ijerph110909897.

Abstract

Mitochondrial toxicity can be one of the most dreadful consequences of exposure to a wide range of external agents including pathogens, therapeutic agents, abuse drugs, toxic gases and other harmful chemical substances. However, little is known about the effects of mitochondrial toxicity on pregnant women exposed to these agents that may exert transplacental activity and condition fetal remodeling. It has been hypothesized that mitochondrial toxicity may be involved in some adverse obstetric outcomes. In the present study, we investigated the association between exposure to mitochondrial toxic agents and pathologic conditions ranging from fertility defects, detrimental fetal development and impaired newborn health due to intra-uterine exposure. We have reviewed data from studies in human subjects to propose mechanisms of mitochondrial toxicity that could be associated with the symptoms present in both exposed pregnant and fetal patients. Since some therapeutic interventions or accidental exposure cannot be avoided, further research is needed to gain insight into the molecular pathways leading to mitochondrial toxicity during pregnancy. The ultimate objective of these studies should be to reduce the mitochondrial toxicity of these agents and establish biomarkers for gestational monitoring of harmful effects.

摘要

线粒体毒性可能是接触多种外部因素(包括病原体、治疗药物、滥用药物、有毒气体和其他有害化学物质)最可怕的后果之一。然而,对于线粒体毒性对接触这些可能具有经胎盘活性并影响胎儿重塑的因素的孕妇的影响,我们知之甚少。据推测,线粒体毒性可能与某些不良产科结局有关。在本研究中,我们调查了接触线粒体毒性物质与因宫内接触导致的生育缺陷、胎儿发育不良和新生儿健康受损等病理状况之间的关联。我们回顾了人体研究的数据,以提出可能与暴露的孕妇和胎儿患者所出现症状相关的线粒体毒性机制。由于一些治疗干预或意外接触无法避免,需要进一步研究以深入了解孕期导致线粒体毒性的分子途径。这些研究的最终目标应该是降低这些物质的线粒体毒性,并建立用于监测有害影响的妊娠生物标志物。

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