Wei Xia, Xiaoling Zhang, Kai Miao, Rui Wang, Jing Xu, Min Guo, Zhonghong Wu, Jianhui Tian, Xinyu Zhang, Lei An
Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture, College of Animal Sciences and Technology, China Agricultural University, Beijing 100094, P. R. China.
J Reprod Dev. 2016 Jun 17;62(3):279-87. doi: 10.1262/jrd.2015-064. Epub 2016 Mar 4.
An increasing number of reports indicate that in vitro fertilization (IVF) is highly associated with long‑term side effects on embryonic and postnatal development, and can sometimes result in embryonic implant failure. While high‑throughput gene expression analysis has been used to explore the mechanisms underlying IVF-induced side effects on embryonic development, little is known about the effects of IVF on conceptus-endometrial interactions during the peri-implantation period. Using sheep as a model, we performed a comparative transcriptome analysis between in vivo (IVO; in vivo fertilized followed by further development in the uterus) and in vitro produced (IVP; IVF with further culture in the incubator) conceptuses, and the caruncular and intercaruncular areas of the ovine endometrium. We identified several genes that were differentially expressed between the IVO and IVP groups on day 17, when adhesion between the trophoblast and the uterine luminal epithelium begins in sheep. By performing Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, we found that, in the conceptus, differentially expressed genes (DEGs) were associated mainly with functions relating to cell binding and the cell cycle. In the endometrial caruncular area, DEGs were involved in cell adhesion/migration and apoptosis, and in the intercaruncular area, they were significantly enriched in pathways of signal transduction and transport. Thus, these DEGs are potential candidates for further exploring the mechanism underlying IVF/IVP-induced embryonic implant failure that occurs due to a loss of interaction between the conceptus and endometrium during the peri-implantation period.
越来越多的报告表明,体外受精(IVF)与胚胎及出生后发育的长期副作用高度相关,有时还会导致胚胎着床失败。虽然高通量基因表达分析已被用于探究IVF对胚胎发育产生副作用的潜在机制,但关于IVF在着床期对孕体 - 子宫内膜相互作用的影响却知之甚少。我们以绵羊为模型,对体内受精(IVO,体内受精后在子宫内进一步发育)和体外生产(IVP,IVF后在培养箱中进一步培养)的孕体以及绵羊子宫内膜的肉阜区和肉阜间区进行了比较转录组分析。我们鉴定出了几个在第17天IVO组和IVP组之间差异表达的基因,此时绵羊的滋养层与子宫腔上皮开始粘连。通过进行基因本体论富集分析和京都基因与基因组百科全书(KEGG)通路分析,我们发现,在孕体中,差异表达基因(DEG)主要与细胞结合和细胞周期相关功能有关。在子宫内膜肉阜区,DEG参与细胞粘附/迁移和凋亡,而在肉阜间区,它们在信号转导和运输通路中显著富集。因此,这些DEG是进一步探究IVF/IVP导致胚胎着床失败机制的潜在候选基因,这种失败是由于着床期孕体与子宫内膜之间相互作用丧失所致。