lncRNA FR383493在射频电磁场致青春期前小鼠睾丸发育时间毒性中的作用机制

射频电磁场(radiofrequency fields, RF)作为一种重要的环境电磁污染物可致睾丸损伤，且儿童对RF更敏感。已知哺乳动物生殖系统存在昼夜节律，24小时中不同时相对RF的敏感性不同，但其调控机制尚不清楚。前期研究中我们发现，lncRNA FR383493可调控生物钟基因转录因子FOXP3的表达。本项目采用时间生物学和生殖发育毒理学相结合的策略，研究RF暴露对青春期前睾丸发育的昼夜时间毒性及其特征。筛选青春期前小鼠睾丸对RF最敏感和最不敏感两个时间窗，通过FISH、 RT-PCR等方法揭示钟基因RORgamma与睾丸发育时间毒性的相关性，并构建低表达和过表达模型探究RORgamma上游调控信号通路FR383493/FOXP3在RF暴露睾丸发育时间毒性中的作用，从而阐明RF暴露对青春期前睾丸发育昼夜时间毒性的发生机制。本研究将为RF暴露引起睾丸发育损害的防治提供新的思路。

As an important environmental electromagnetic pollutant，radiofrequency field (radiofrequency field, RF) radiation has been reported to cause damage in testes, and children are more sensitive to RF exposure than adults. Circadian rhythms of the reproductive system have been widely demonstrated in mammals, which result in different sensitivities of testes to RF at different periods of a day, however, the mechanisms underneath this effect remain unknown. Previously we demonstrated that lncRNA FR383493 interacts with the transcriptor FOXP3 of clock genes. This project is to study the testis development chronotoxicity induced by RF with the combination of chronobiology and reproductive development toxicology. The circadian peak and trough time points of RF induced toxicity will be recognized and the clock gene RORγ of mice exposed to RF will be determined by FISH assay and Realtime PCR. By establishing lncRNA low and over expression models, the function of lncRNA FR094548/FOXP3 signaling pathways, at the upstream of the clock gene RORγ, in the testicular development chronotoxicity due to RF exposure will be explored to elucidate the molecular mechanisms of chronotoxicity induced by RF in the prepubertal mice testis. This project is expected to inspire novel countermeasures against the male testicular development malfunction caused by RF on prepubertal mice.