PAHs暴露与儿童青春发动时相提前的相关性研究

Earlier puberty timing is a currently important health issue drawing global attention, which has major impact on children’s physiology, personality, cognition and behavior. However, the mechanism inducing earlier puberty is not clear. Previous studies indicated that environmental endocrine disruptors (EEDs) were closely associated with puberty timing. Polycyclic aromatic hydrocarbon (PAHs) is a kind of strong toxic EEDs with high pollution load in the children’s body, which can interfere sex hormone secretion and affect reproductive function. But the impact of PAHs exposure on puberty has not been reported yet. Based on the results of baseline survey, the study will identify the PAHs exposure of the children, and then 1020 children will be recruited to form the development cohort. Four kinds of PAHs metabolite concentration of these children will be monitored regularly to estimate the exposure levels, and their sexual development progression will be measured by physical examinations and pubertal development scales. This study will observe the initiation and progression of pubertal development from the perspective of the continuous development, and analyze the interference effects of PAHs exposure on puberty timing of children and the critical period, which aims to further enrich the study theory of health effects of environment factors. The results of the study will be of great importance in revealing the reasons for earlier puberty timing, and will also provide thinking methods for the prevention and control of earlier puberty timing caused by EEDs.

青春发动时相提前是当前全球普遍关注的重要健康问题，对儿童生理、人格、认知和行为等方面有重要影响，但青春发动时相提前的诱发机制尚不清楚。研究表明环境内分泌干扰物（EEDs）与青春发动时相密切相关，而多环芳烃（PAHs）是儿童体内污染负荷较高的一类强毒性EEDs，可干扰性激素分泌影响生殖功能，但PAHs对青春期发育的影响尚未见报道。本研究在基线调查基础上，确定对象儿童PAHs暴露水平，从中选取1020名儿童建立发育队列，进行双向性队列研究，定期监测尿液中4种PAHs代谢物浓度以估计其内暴露水平，并通过体格检查和青春发育事件量表追踪性发育过程。本研究从连续发展的视角追踪儿童青春期发育的启动与进程，分析PAHs暴露对青春发动时相的干扰效应及其作用的关键期，旨在进一步丰富环境因素健康效应的研究理论，研究结果对于揭示当前青春发动时相提前的原因具有重要意义，也为防治EEDs所致青春发动时相提前提供思路。

以前期建立的1237名1-4年级儿童青春发育队列为基础，对其继续进行每半年1次为期3年的随访，分析对象儿童各青春发育事件的启动和进程，研究结果显示，女童乳房、阴毛、腋毛发育启动和月经初潮的中位数年龄分别为9.98岁、11.40岁、11.93岁和11.65岁；女童乳房、阴毛发育从启动到成熟分别需要约2.76年和2.04年；女童月经初潮、乳房发动提前率分别为40.3%、1.3%。男童首次遗精、外生殖器、睾丸、阴毛、胡须和腋毛发育启动中位数年龄分别为12.15岁、10.43岁、11.26岁、12.15岁、12.22岁和13.18岁；睾丸由启动（4ml）发育至成熟（12ml）需要1.43年；男童首次遗精和睾丸发动提前率分别为81.3%和4.9%。同时，本研究建立了儿童多环芳烃（PAHs）暴露队列，观察PAHs暴露与儿童青春发动时相的关系，Cox回归分析发现，1-羟基芘和9-羟基菲可能是女童月经初潮提前的危险因素；2-羟基芴和9-羟基菲可能是男童睾丸发育和首次遗精提前的危险因素。此外，本研究还发现儿童青春早期肥胖、高心理应激水平、母亲月经初潮年龄及不良家庭结构等均可能影响儿童青春发动时相。由于队列中启动青春发育的人数有限（尤其是男童），这些因素与青春发动时相的确切关系还需继续随访观察加以证实。本研究结果反映了男女童各青春发育事件的启动和发展规律，也为预防儿童青春发动时相提前提供了思路和依据。