人类辅助生殖技术来源胎盘全基因组表达谱研究  

Altered Global Gene Expressions of Human Placenta Subjected to Assisted Reproductive Technology Treatments

作　　者：张园[1,2] 崔毓桂[1] 周作民[2] 沙家豪[2] 李瑛[3] 刘嘉茵[2] 

机构地区：[1]南京医科大学第一附属医院生殖医学科,210029 [2]南京医科大学江苏省生殖医学重点实验室 [3]江苏省计划生育科学技术研究所

出　　处：《国际生殖健康/计划生育杂志》2011年第2期80-87,I0001,共9页Journal of International Reproductive Health/Family Planning

基　　金：国家973项目(2006CB94405计划和2007CB948103);江苏省科技计划项目(BM2008151)

摘　　要：目的:通过比较辅助生殖技术(ART)来源和自然妊娠来源胎盘全基因组表达谱的差异,研究ART技术对胎盘功能和胎儿发育的影响,借此评估ART子代的安全性。方法:胎盘组织取自因输卵管因素行体外受精-胚胎移植和自然妊娠足月产妇各3例。利用AffymetrixHG-U133 Plus 2.0基因芯片对2组胎盘组织进行芯片杂交分析。用定量反转录聚合酶链反应(qRT-PCR)验证其中10个差异表达基因,根据其涉及的不同功能进行生物信息学分析。分为6类:免疫应答、跨膜转运、代谢、氧化应激、细胞分化及其他功能。用免疫组织化学对其中5个差异表达基因产物进行细胞定位研究。结果:ART来源胎盘组织中共鉴定出26个差异表达基因,其中17个上调,9个下调。其中涉及免疫应答的基因,如ERAP2和STAT4;涉及细胞分化的基因如MUC1,经qRT-PCR验证2组间确实存在差异表达。基因产物主要表达在胎盘绒毛组织中,分布在合体滋养层细胞的细胞质和(或)细胞膜中。结论:ART来源胎盘和自然妊娠胎盘存在全基因组表达谱差异。差异表达基因涉及到多种胎盘关键功能,ERAP2,STAT4及MUC1等差异表达基因可能作为评估胎盘与ART子代安全性关联的分子标记物。Objective: To investigate the global gene expression alteration between the placentae undergoing assisted reproductive technology(ART) manipulation and the placenta derived from natural pregnancy,thus reflecting the association between such procedures and the ensuing offspring health.Methods: Three term placenta samples were obtained from patients who underwent in vitro fertilization and embryo transfer because of oviductal factors,along with three taken from those underment normal pregnancy.A Gene Chip Affymetrix HG-U133 Plus 2.0 Array was utilized to view and analyze the genes.By means of qRT-PCR,we certified microarray data from 10 of the dysregulated genes,5 of which we located,through immunohistochemistry,more precisely in the placenta.Results: Twenty-six differentially expressed genes were identified in the ART-treated placentae: 17 up-regulated;9 down-regulated.Eighteen of these were classified into six groups according to critical placental functions: immune response;transmembrane transport;metabolism;oxidative stress;cell differentiation;and a body of other functions.Genes involved in immune response,such as ERAP2 and STAT4,as well as those regulating cell differentiation,such as MUC1,were discerned to be differentially expressed.These were located in the placental villus tissues,in either the cytoplasm or the membrane of syncytiotrophoblastic cells.Conclusions: Differentially extressed genes in the placentae derived from ART treatment have been certified in our study.Abnormal profiles of critical placental function genes,such as ERAP2,STAT4 and MUC1,may be valuable in understanding how the placenta affects fetal programming,along with possible associations between ART treatment and offspring health.

关 键 词：基因组 人 芯片分析技术 生殖技术 辅助 胎盘 自身免疫 

分 类 号：R714.8[医药卫生—妇产科学]