多环芳烃在母亲-胎儿间传递的研究

With the development of economy and society, various pollutants threaten human health and have attracted lots of research attention. Pregnant women are special populations menanced by the pollutants. The exposure to environmental pollutants in daily life and work may cause adverse pregnancy outcomes.We need to find a scientific way to correlate the common factors of environmental pollution and adverse pregnancy. The first step is to clarify the pollutants transfer from mother to fetus. This project selects polycyclic aromatic hydrocarbons (PAHs) as the representation of pollutants, which are a group of chemicals mostly produced due to incomplete combustion of fossil fuels. PAHs are ubiquitous in the environment as persistent organic pollutants, and could induce a variety of toxic effects in human body, including reproductive toxicity, which will increase adverse pregnancy outcomes. The ubiquitous nature of PAHs calls for the urgent work to find out the toxicity mechanism to human body caused by PAHs. To clarify the relationship between PAHs and associated adverse outcomes, we will firstly need to find out the way how PAHs passed through the mother to the fetus and caused the fetal prenatal exposure. The commonly used chemical quantification method provided PAHs accumulation data in human body, without the exposure history and transfer from mother to fetus. This project is proposed to use chemical and biological endpoints to study PAHs transfer from mother and fetus. Chemical quantitative methods will be applied to detect PAH concentrations in matched samples of the maternal peripheral blood, placenta and fetal cord blood. Meanwhile, taking into account of the metabolism of PAHs in human body, this research will combine a variety of biological evidences (PAHs-DNA adducts, cell micronuclei rate, metabolic enzyme gene polymorphism) to reveal PAHs exposure history, level of metabolism and metabolites transfer. The combined evidences are very helpful to investigate the behavior and risk of PAHs, to provide a new point of view for the scientific elucidation of PAHs in the mother - fetus transfer. This study will also lay a solid foundation for the study of the link between adverse pregnancy and environmental pollution.

多环芳烃（PAHs）作用于人体产生多种毒性效应，包括产生生殖毒性，增加不良妊娠风险。其在环境中的普遍存在使对PAHs于人体致毒机制的认识刻不容缓。要明确PAHs与不良妊娠发生之间的关系，首先需要明确PAHs如何通过母体传递到胎儿造成胎儿产前暴露，即母体-胎儿间的传递。传统的化学定量获得的人体中PAHs浓度信息不能反映母体对PAHs的历史暴露和母体-胎儿的传递。本研究针对此问题，拟通过纯化学定量测定相匹配的母体外周血、胎盘、胎儿脐带血中PAHs的浓度。同时，考虑PAHs在体内的代谢，结合多种生物学证据（多环芳烃-DNA加合物、细胞微核率、代谢酶基因多态性等），以反映多环芳烃暴露历史、代谢水平及代谢物的传递。化学与生物手段的复合证据能对PAHs的行为和风险有更深的认识，为科学的阐明PAHs在母亲-胎儿间的传递提供新的思路，为研究不良妊娠与环境污染之间的联系打好坚实的基础。

多环芳烃（Polycyclic aromatic hydrocarbons, PAHs）是一类广泛存在于环境、能在多种环境介质中长距离迁移、不易降解，具有持久性污染能力的典型环境污染物。由于其具有免疫毒性、神经毒性、生殖和发育毒性以及“三致”作用而引起了社会的广泛关注。本研究通过检测昆明及其周边地区非特殊暴露人群母血、胎盘和脐带血配对样本中美国环境保护署优先控制的16种PAHs浓度，并通过不同组织中PAHs浓度的对比，分析PAHs在不同组织、或相同组织对照组与病例组间的含量差异，结合母胎体系中PAHs代谢酶基因多态性，探讨PAHs在母胎体系中的代谢及传输的影响，及其对妊娠并发症发病的影响。本研究是云南省内第一项报道非特殊暴露人群母血、胎盘和脐血配对样本内PAHs浓度、来源、分布、传输及其对病理妊娠影响的病例对照研究。研究发现：昆明地区非特殊暴露产妇体内的PAHs主要来自于热解源（即有机物的不完全燃烧或热解）、以HMW PAHs为主。通过比较同类人群不同组织/器官（母血、胎盘和脐血）和不同类人群相同组织器官中PAHs的浓度，发现胎盘屏障对LMW PAHs可能不具有屏蔽作用，而健康的胎盘则可能对HMW PAHs具有屏障功能，能将其截留并储存在胎盘中；受病理妊娠影响的胎盘，则不具有截留和储存HMW PAHs的能力（或其能力较弱），表明病理妊娠患者胎盘的屏障功能可能受到了破坏。本研究没有观察到病理妊娠患者体内的LMW PAHs、HMW PAHs、7种致癌PAHs或总PAHs随着疾病严重程度的增加而增加的趋势，表明非特殊暴露人群正常生活中暴露的低剂量的PAHs可能不是病理妊娠发病的主要致病因素。通过相关代谢酶基因多态性分组比较发现，基因型为CYP1A1杂合突变-GSTM1缺失型、CYP1A1 杂合突变-GSTT1存在型和CYP1A1杂合突变-CYP2E1杂合型、CYP2E1杂合-GSTM1缺失型病理妊娠患者均表现为母血和脐血内的Σ16PAHs含量高于对照组，而胎盘中的Σ16PAHs浓度则低于对照组。但这些基因型并没有表现出一致的规律（均突变、缺失或野生、存在），表明病例组和对照组组织样本间的PAHs含量差异可能不是由代谢引发的。