Center of Clinical Reproductive Medicine, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China.
Placenta. 2010 Apr;31(4):251-8. doi: 10.1016/j.placenta.2010.01.005. Epub 2010 Jan 29.
Researchers are more and more concerning the safety of fetus or offspring derived from assisted reproductive technology (ART) treatment. As the placenta is a critical organ that sustains and protects the fetus, we hypothesize that altered global gene expression of the placenta subjected to ART manipulation may reflect changes associated with ART procedures and subsequently causal related to offspring health.
Three term placenta samples were obtained from patients undergone in vitro fertilization and embryo transfer due to oviductal factors only. Other three control placentae were from those underwent normal pregnancy. A GeneChip Affymetrix HG-U133 Plus 2.0 Array was utilized to analyze the genes. Using qRT-PCR we certified microarray data from 10 dysregulated genes. Five genes were localized precisely in the placenta as per immunohistochemistry.
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 function: immune response; transmembrane transport; metabolism; oxidative stress; cell differentiation; and other functions. Genes involved in immune response, such as ERAP2 and STAT4, and those regulating cell differentiations, such as MUC1, were discerned to be differentially expressed. These gene products were expressed in the placental villus tissues, either in the cytoplasm or in the membrane of syncytiotrophoblastic cells.
To our knowledge, this is the first study in comparing differentially expressed genes in placentae from patients undergone ART treatment vs. those underwent normal pregnancy. Abnormal profiles of critical placental functioning genes, such as ERAP2, STAT4 and MUC1, may be valuable biomarkers to understand how the placenta affects fetal development and ART-derived offspring's health problems.
研究人员越来越关注辅助生殖技术（ART）治疗中胎儿或后代的安全性。胎盘是维持和保护胎儿的关键器官，我们假设接受 ART 操作的胎盘的整体基因表达发生改变，可能反映了与 ART 程序相关的变化，并随后与后代的健康有关。
从因输卵管因素接受体外受精和胚胎移植的患者中获得三个足月胎盘样本。另外三个对照组胎盘来自正常妊娠的患者。使用 Affymetrix HG-U133 Plus 2.0 基因芯片分析基因。使用 qRT-PCR 我们从 10 个失调基因的微阵列数据中进行了验证。根据免疫组织化学，将 5 个基因精确定位在胎盘上。
在 ART 处理的胎盘中鉴定出 26 个差异表达基因：17 个上调；9 个下调。其中的 18 个根据胎盘的关键功能分为六个组：免疫反应；跨膜转运；代谢；氧化应激；细胞分化；和其他功能。参与免疫反应的基因，如 ERAP2 和 STAT4，以及调节细胞分化的基因，如 MUC1，被发现差异表达。这些基因产物在胎盘绒毛组织中表达，要么在细胞质中，要么在合体滋养细胞的膜中。
据我们所知，这是首次比较接受 ART 治疗的患者与接受正常妊娠的患者胎盘之间差异表达基因的研究。异常的关键胎盘功能基因谱，如 ERAP2、STAT4 和 MUC1，可能是理解胎盘如何影响胎儿发育和 ART 后代健康问题的有价值的生物标志物。
