孕期镉暴露后子代成年卵巢颗粒细胞激素合成基因相关microRNA表达谱改变  

Changes in Expression Profile of Hormone Synthesis Gene-Related microRNAs in Adult Ovarian Granulosa Cells of Offspring after Cadmium Exposure During Pregnancy

作　　者：刘张嫔 李庆宇 吕亚可 李静雯 张文昌 LIU Zhangpin;LI Qingyu;LYU Yake;LI Jingwen;ZHANG Wenchang(Department of Preventive Medicine,School of Public Health,Fujian Medical University,Fuzhou 350122,China)

机构地区：[1]福建医科大学公共卫生学院预防医学系,福州350122

出　　处：《福建医科大学学报》2021年第4期278-282,共5页Journal of Fujian Medical University

基　　金：国家自然科学基金项目(81673212)。

摘　　要：目的分析孕期镉暴露子代大鼠成年后卵巢颗粒细胞中靶向雌孕激素合成相关基因的microRNA(miRNA)表达谱的变化情况,为进一步探讨子代卵巢激素分泌功能损害的表遗传调控机制提供依据。方法SPF级SD大鼠孕期全程暴露于0、8 mg/kg氯化镉,产F1代。F1雌性子代与新购健康雄性大鼠交配,产F2代。提取F1、F2代成年大鼠卵巢颗粒细胞,制备miRNA芯片。通过miRNA芯片差异表达分析(两种标准)、结合数据库和文献筛选出可能调控子代雌孕激素合成的miRNAs,并进行生物信息学分析(GO和KEGG分析)。结果根据两种标准的芯片筛选结果、数据库比对和文献检索,F1代分别筛选出25、2个目的miRNAs;F2代分别筛选出20、4个miRNAs。生物信息学分析表明,目的miRNAs参与孕激素介导的卵母细胞成熟、MAPK信号通路、cAMP信号通路等过程。结论miRNA可能在孕期镉暴露子代雌孕激素合成障碍中起重要调控作用;部分miRNAs出现代际效应;虽两代子代孕酮水平均下降,但机制存在差异。Objective To analyze the changes of microRNA(miRNA)expression profiles targeting estrogen and progesterone synthesis-related genes in ovarian granulosa cells of cadmium-exposed offspring rats during pregnancy as adults and provide basis exploration for the epigenetic mechanism of ovarian damage in offspring.Methods SPF grade SD rats were exposed to 0 or 8 mg/kg cadmium chloride throughout pregnancy to produce the F1 generation.F1 female offspring and newly purchased healthy male rats were mated to produce F2 generation.Ovarian granulosa cells from F1 or F2 adult rats were extracted to prepare miRNA microarrays.miRNAs that may regulate estrogen and progesterone synthesis in offspring were selected by miRNA microarray differential expression analysis(two criteria),combined with databases and literature,and subjected to bioinformatics analysis(GO and KEGG analysis).Results In total,25 or 2 target miRNAs were selected in the F1 generation;20 or 4 miRNAs were selected in the F2 generation,respectively.The results of bioinformatics analysis showed that the target miRNAs are involved in progestogen-mediated oocyte maturation,MAPK signaling pathway,cAMP signaling pathway,etc..Conclusion miRNAs may play an important role in the regulation of estrogen and progesterone synthesis disorders in offspring exposed to cadmium during pregnancy.Some miRNAs showed intergenerational effects;although the levels of progesterone in the offspring of the two generations have decreased,the possible mechanisms are different.

关 键 词：镉 颗粒细胞 microRNA 雌孕激素 子代 

分 类 号：R114[医药卫生—卫生毒理学]