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作 者:成金鑫 夏超[2] 张浩[1] 付国庆[1] 易玲娜 全超 周婷[1] 张玲[1] 石玉琴[1] CHENG Jin-xin;XIA Chao;ZHANG Hao;FU Guo-qing;YI Ling-na;QUAN Chao;ZHOU Ting;ZHANG Ling;SHI Yu-qin(Environmental Toxicology Laboratory,Hubei Province Key Laboratory of Occupational Hazard Identification and Control,School of Public Health,Wuhan University of Science and Technology,Wuhan,Hubei 430065,China;Ezhou Center for Disease Control and Prevention,Ezhou,Hubei 436000,China)
机构地区:[1]武汉科技大学公共卫生学院环境毒理学研究室/职业危害识别与控制湖北重点省实验室,湖北武汉430065 [2]鄂州市疾病预防控制中心,湖北鄂州436000
出 处:《中华男科学杂志》2022年第9期779-785,共7页National Journal of Andrology
基 金:湖北省高等学校优秀中青年科技创新团队项目(T2020003)。
摘 要:目的:研究镉对大鼠睾丸组织piRNA表达的影响及其可能的机制。方法:将6周龄的12只SD大鼠利用随机数表分为对照组和镉染毒组,对照组用生理盐水进行灌胃,镉染毒组用CdCl2染毒液[3 mg/(kg·d)]进行灌胃染毒,28 d后收集睾丸组织,采用CASA精子分析系统记录精子浓度及活力,利用基因芯片进行piRNA测序,对差异piRNA进行生物信息学分析。结果:与对照组相比,镉染毒组大鼠的精子浓度和活力都显著降低(P<0.05),睾丸组织中有272个piRNA表达上调,402个piRNA表达下调,经验证,4个上调的piRNA表达结果与基因芯片结果一致。生物信息学分析结果表明,4个上调的piRNA靶基因参与细胞凋亡过程的负调控、基因表达的正调控、GTPase活性正调控等50个生物过程,主要富集于癌症中的转录失调、钙信号通路、丝裂原活化蛋白激酶信号通路等13个信号通路中,其中piRNA-DQ765261与Bcl-2有结合位点。结论:镉可引起大鼠睾丸组织中piRNA表达改变,其中某些piRNA可能在精子的自噬和凋亡过程中起着重要的作用,Bcl-2可能是piRNA-DQ765261的靶点。Objective:To study the impact of cadmium(Cd)on the expressions of PIWI-interacting RNAs(piRNA)in the rat testis and its possible action mechanism.Methods:Twelve 6-week-old SD rats were randomly divided into a Cd-exposure and a control group,the former gavaged with CdCl2at 3 mg/kg/d and the latter with normal saline,all for 28 successive days.Then the testicular tissues were collected from the rats,sperm concentration and motility were obtained by computer-assisted sperm analysis(CASA),and piRNA sequencing was performed using the gene chip,followed by bioinformatics analysis of differentially expressed piRNAs.Results:Compared with the controls,the rats in the Cd-exposure group showed significantly decreased sperm concentration and motility(P<0.05).The expressions of 272 piRNAs were up-regulated and 402 down-regulated after 28 days of Cd exposure,and 4 of the up-regulated piRNAs were consistent with the results of gene chip verification.Bioinformatics analysis showed that the 4 up-regulated piRNA target genes were involved in 50 biological processes,such as negative regulation of apoptosis,positive regulation of gene expression and positive regulation of GTPase activity,and mainly concentrated in 13 signaling pathways including transcription dysregulation,calcium and mitogen-activated protein kinase signaling pathways in cancer.Among them,PIRNA-DQ765261 had a binding site with Bcl-2.Conclusion:Cadmium can induce changes in the expressions piRNAs in the rat testicular tissue,and some piRNAs may be involved in the autophagy and apoptosis of sperm.Bcl-2 may be the target of PIRNA-DQ765261.
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