Transcriptomic signatures in trophectoderm and inner cell mass of human blastocysts with different expectations of pregnancy

Abstract

Selection of high-quality embryos is important to achieve successful pregnancy in assisted reproductive technology (ART). Recently, it has been debated whether RNA-sequencing (RNA-seq) should be applied to ART to predict embryo quality. However, the information on which genes can serve as markers for pregnant expectancy is limited. Furthermore, there is no information on which transcriptome of trophectoderm (TE) or inner cell mass (ICM) is more highly correlated with pregnant expectancy. Here we performed RNA-seq analysis for TE and ICM, respectively, in human blastocysts of which the expectation of pregnancy was retrospectively determined by the clinical outcomes of 1,890 cases of frozen-thawed blastocyst transfer. We identified dozens of genes that were correlated with the expected pregnancy rate in ICM and TE, respectively, with a larger number of genes identified in TE. Importantly, downregulated genes in TE of blastocysts that were estimated to have lower expectation of pregnancy included tight junction-related genes, such as CXADR, CLDN10, and ATP1B1, which were implicated in peri-implantation development. Additionally, we showed that aneuploidy estimation by RNA-seq datasets does not correlate with pregnancy expectation. Our study thus provides an expanded list of candidate genes for prediction of pregnancy in human blastocyst embryos.