塑化剂暴露与儿童性别角色发展关联的前瞻性队列研究

In recent years, the phenomenon of gender role of the opposite sex showed an increasing trend in China. There was lack of study on the effects of PAEs on children’s gender role, especially the cohort study of the associations between PAEs exposed and the development of gender role during puberty had not been reported yet. Based on our exist cohort of blood pressure in child and adolescent, the children’s sex role inventory was carried out for all the students in the cohort. Also, the urine samples were also collected at three time points, and were detected on the content of seven metabolites of PAEs in urine. The associations of the distribution of children’s gender role and the metabolites of PAEs in urine were analyzed. The subjects were selected from 11 to 12 years boys aged and 10 to 11 years girls with the complete data of baseline characterize and the metabolites of PAEs, and the urine samples at three time points and the children’s sex role inventory were collected in each year. Then we observed the change of the distribution of the percentage of Masculinity, feminization, androgyny and undifferentiation. Using the blood samples of exist cohort, the methylation of Alu repeats was detected by Gene array mass spectrum analysis system of MassARRAY Analyzer 4.0. This study was designed to explore the role of methylation in the epigenetic mechanism of PAEs exposed on the development of the children’s gender role, and to provide the environmental evidence for the effects of PAEs exposed on gender role in prospective cohort study.

近年来，我国儿童青少年性别角色异性化的现象快速增加。目前关于PAEs影响儿童性别角色发展的人体研究较为缺乏，尤其是PAEs暴露与青春期性别角色改变关联的前瞻性队列尚未见报道。基于已有的儿童青少年血压队列，本项目采用儿童性别角色量表对队列人群进行调查，收集儿童早、中、晚三个时间点的尿液，检测尿中PAEs 7种代谢物含量，分析被调查地区儿童性别角色的分布及其与PAEs暴露的关联。筛选基线特征、PAEs代谢物资料完整的11～12岁男生、10～11岁女生约800名作为前瞻性队列的研究对象，连续随访3年，每年收集3个时间点的尿液和完成一次儿童性别角色量表，观察男、女生中男性化、女性化、双性化、未分比例的变化规律，利用队列已有血样，采用基因阵列质谱分析系统检测Alu重复序列的甲基化水平，探究甲基化在PAEs暴露影响儿童性别角色发展中的表观遗传机制，获得PAEs暴露影响儿童性别角色改变的环境证据。

近年来，我国儿童青少年的性别角色发展备受社会关注。目前关于环境PAEs影响儿童性别角色发展的人体研究较为缺乏，尤其是PAEs暴露与青春期性别角色改变关联的前瞻性队列尚未见报道。基于厦门市儿童血压队列的基础上，将队列中体检档案和生物样本资料完整的两所小学二至四年级823名小学生纳入为队列随访对象，分别在2018年5月、2019年5月和2020年10月（疫情延误）采用儿童性别角色量表（CSRI中文版）对所有研究对象进行调查，观察男、女生中男性化、女性化、双性化、未分化比例的演变规律，监测儿童性别角色早期发展情况；通过体格检查和调查问卷获得研究对象人口特征和既往疾病史，收集3个随访时间点的晨尿，检测尿中PAEs7种代谢物含量[邻苯二甲酸单甲酯(MMP)、邻苯二甲酸单乙酯(MEP)、邻苯二甲酸单丁酯(MnBP)、邻苯二甲酸单异丁酯(MiBP)、邻苯二甲酸单（2-乙基-己）酯（MEHP）、邻苯二甲酸单（2-乙基-5-氧己基）酯（MEOHP）和邻苯二甲酸单（2-乙基-5-羟基己基）酯（MEHHP）]，分析被调查地区儿童性别角色的分布及其与PAEs暴露的关联。研究发现我国城市儿童性别角色以双性化（39.1%）为主，未分化（36.2%）和异性化（7.0%）的比例较高，提示儿童性别角色早期发展不容乐观；城市儿童至少检出3种PAEs代谢产物，提示我国城市儿童普遍暴露于PAEs，需要引起高度重视；另外研究发现家庭因素（家庭结构、社会经济地位、独生子女）、父母教养方式、环境PAEs代谢物浓度与儿童性别角色早期发展密切相关，应重视儿童成长的早期环境，促进性别角色的健康发展。在上述研究基础上，研究团队将进一步利用队列已有血样，采用基因阵列质谱分析系统检测LOXL3、SLC6A19基因的DNA甲基化水平，探究甲基化在PAEs暴露影响儿童性别角色发展中的表观遗传机制，研究成果在国内外期刊发表论文14篇，其中SCI论文13篇，会议报告3次，硕士研究生和博士研究生学位论文各1篇。

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