多囊卵巢综合征风险与环境地球化学控制因素相关性研究

Environmental endocrine disruptors (EEDs) widely spread in environmental media, and can enter into the human body through different ways and enrich in vivo. Because of their hormone like or anti-hormone effect, they can interfere with normal hormone function, and cause a variety of endocrine and metabolic diseases. Besides, it can also affect human and their offspring's healthy extremely. Polycystic ovary syndrome (PCOS) is one of the most common diseases of reproductive endocrinology and metabolism. Its prevalence increased in recent years, and this might be associated to EEDs. Previous and our preliminary studies indicate that serum levels of some EEDs elevated in PCOS patients, which indicated environmental geochemical behavior of EEDs might dominate the association between EEDs and PCOS. However, it's difficult to breakthrough in the influence of environmental aspect. This study is going to combine the medicine and environmental geochemistry involving EEDs characteristics. We plan to detect the levels typical EEDs (including BPA,PAEs,PBDEs) in different environmental matrices ( air,soil, water ) and human serum by Gas Chromatography/Mass Spectrometry (GC-MS) in Chengdu, where the incidence of PCOS is one of the highest city. And then, according to the results of population exposure, absorbing status, to reveal the inherent association among environmental EEDs exposure levels, ways of exposure, absorbed dosage, EEDs serum levels in vivo and the risk of PCOS. With this we can explore the role of environmental geochemical controlling factors in the risk of PCOS, and provide theoretical basis for reducing the risk of PCOS.

环境内分泌干扰物在环境介质中广泛存在,通过不同途径进入人体并富集，表现出拟激素或抗激素的作用，干扰正常性激素功能,引发各种内分泌代谢疾病，严重影响人类及子代的健康。多囊卵巢综合征是最常见的生殖内分泌和代谢疾病，近年患病率不断攀升,其患病风险可能与EEDs相关。既往及本课题组前期研究发现PCOS患者血清某些EEDs升高，提示EEDs的环境地球化学行为可能主导它们之间的相关性。但目前临床及流行病学在环境影响方面难有突破。本研究拟将环境和健康两个学科结合，利用GS-MS法对成都这一PCOS高发地区环境基质(空气、土壤、水)和人血清中EEDs(BPA、PAEs、PBDEs)进行检测，结合研究人群的暴露、吸收状态，揭示环境EEDs暴露水平-暴露途径-吸收剂量-血清EEDs水平-PCOS患病风险间的内在关联，探讨EEDs的环境地球化学控制因素在PCOS患病中的作用,为降低PCOS患病风险提供理论依据。

多囊卵巢综合征（PCOS）目前病因不清，多认为遗传和环境因素协同作用影响PCOS的发生，而环境因素中环境内分泌干扰物（EEDs）在环境介质中广泛存在，并可通过各种途径到达人体蓄积；然而EEDs的环境地球化学分布特征与PCOS患病的关系未能揭示。为探讨 EEDs 与 PCOS 患病风险之间的相关性，从环境源头减少PCOS发病率和患病率，对PCOS患病风险的预防和控制提供理论依据，本项目利用环境与健康的交叉融合优势，首次在国内采用标准的临床流行病学方法对基于社区人群进行大样本的抽样调查，评估成都市不同区域PCOS发病情况差异，同时采用气相质谱色谱法（GC-MS）对人群少量血清和相应环境介质中主要的三类EEDs（多溴联苯醚、邻苯二甲酸酯、双酚A）含量进行同时检测，采用环境污染物暴露评估模型，个体化评估人群环境内分泌干扰物的外暴露、内暴露水平，并结合环境污染物暴露方式，探讨体外 EEDs 暴露水平、体内血清 EEDs 水平和 PCOS 患病风险之间的关系。本研究发现：成都市不同区域PCOS患病率存在差异，同时环境介质及人群血清中三类EEDs含量分布均存在一致性，即EEDs含量均以PAEs为主，其次为双酚A，最低为PBDEs；成都市女性人群血清中PBDEs、PAEs、BPA检出率范围为90.91%-100%，提示其暴露较普遍；成都市不同区域环境介质中多种EEDs含量、EEDs外暴露水平与血清内暴露水平呈正相关，并均与PCOS患病率呈正相关；PCOS患者血清中PBDEs、PAEs内暴露水平和水来源PBDEs吸收率、土壤来源PBDEs吸收率均高于对照组（P<0.05）。多因素分析提示：血清 PBDEs含量（OR=2.195，P=0.000）、血清 PAEs含量（OR =1.538，P=0.000）是 PCOS发病风险增高的相关因素。本研究提示环境中介质中多种EEDs可能通过各种途径达到人体蓄积，并可能与 PCOS 发病相关。