长链非编码RNA参与尿道下裂雄鼠雄激素的调控  

Long non-coding RNA participates in the regulation of androgen in hypospadiac male rats

作　　者：冯笑 黄恩馥 周云[2] FENG Xiao;HUANG En-Fu;ZHOU Yun(Center for Experimental Animals of Suzhou University,Suzhou 215000,Jiangsu,China)

机构地区：[1]苏州大学实验动物中心,江苏苏州215000 [2]苏州大学附属儿童医院泌尿外科

出　　处：《吉林医学》2024年第6期1275-1279,共5页Jilin Medical Journal

基　　金：江苏省临床医学科技专项基金[项目编号:BL2012051];苏州市民生科技项目[项目编号:SS201754]。

摘　　要：目的:探讨雄性大鼠生殖结节中长链非编码RNA(LncRNA)在邻苯二甲酸二丁酯(DBP)诱导雄性大鼠尿道下裂形成中对雄激素调控的影响。方法:在孕鼠孕13~18 d时按体重800 mg/kg DBP溶于1 ml玉米油灌胃,对照组给予玉米油1 ml/d。于孕19 d时取出胎鼠,分别取下两组雄性胎鼠的生殖结节,进行全转录组基因测序。对测序结果中LncRNA进行筛选、差异分析和功能预测,再筛选8条LncRNA用qRT-PCR验证其表达量。结果:与对照组比较,尿道下裂组生殖结节中有598个差异mRNA,427个差异LncRNA,8条LncRNA差异趋势与测序结果一致,不存在差异趋势与测序结果的差异趋势相反的LncRNA。RT-PCR结果与测序结果一致。共筛选出与雄激素相关的差异表达LncRNAs 130个,与雄激素生物合成途径相关11个,与雄激素受体信号通路的负调控相关25个,与雄激素结合相关10个,与雄激素受体信号通路激活前列腺诱导相关29个,与雄激素代谢过程相关23个,与雄激素受体结合相关16个,与雄激素受体信号通路的正调控相关3个。结论:DBP诱导的尿道下裂雄性大鼠与正常雄性大鼠比较,其生殖结节中LncRNA可通过调控雄激素的合成、代谢、结合,雄激素受体的结合,雄激素受体信号通路这几个方面参与尿道下裂的形成。Objective To investigate the effect of long non-coding RNA(LncRNA)in the genital tubercle of male rats on androgen regulation in the formation of hypospadias of male rats induced by dibutyl phthalate(DBP).Method The pregnant rats were gived 800mg/kg DBP dissolved in 1ml corn oil in the 13 to 18 days of pregnancy to establish model of hypospadias,the pregnant rats in control group gived only 1 ml/d corn oil.Fetal rats were took out from pregnant rats for 19 days of pregnancy.Removed the genital tubercles of male fetal rats and complete whole transcriptome gene sequencing.Analyzed and screened the sequencing result of LncRNA and did function prediction.Finally chose eight LncRNAs to validate their level of expression by qRT-PCR.Results The sequencing results showed that compared with control group,the hypospadias group had 598 differential expression mRNA,427 differential expression LncRNAs.The differential trend of 8 lncRNAs was consistent with the sequencing results,and there was no lncRNA with a differential trend opposite to the sequencing results.The RT-PCR results were consistent with the sequencing results.A total of 130 differentially expressed LncRNAs related to androgens were screened,including 11 related to androgen biosynthesis process,25 related to negative regulation of androgen receptor signaling pathway,10 related to androgen binding,29 related to activation of prostate induction by androgen receptor signaling pathway,23 related to androgen metabolism process,16 related to androgen receptor binding,and 3 related to positive regulation of androgen receptor activity.Conclusion Compared with normal male rats,LncRNA in genital tubercle of hypospadiac male rats induced by dibutyl phthalate participates in the formation of hypospadias by regulating androgen synthesis,metabolism and binding,androgen receptor binding and androgen receptor signaling pathway.

关 键 词：邻苯二甲酸二丁酯 尿道下裂 长链非编码RNA 雄激素 

分 类 号：R34[医药卫生—基础医学]