Comparative Transcriptomic Analysis of Embryo Implantation in Mice and Rats

Abstract

Background/Aims: Embryo implantation is an essential process for eutherian pregnancy, but this process varies across eutherians. The genomic mechanisms that led to the emergence and diversification of embryo implantation are largely unknown. Methods: In this study, we analyzed transcriptomic changes during embryo implantation in mice and rats by using RNA-seq. Bioinformatics and evolutionary analyses were performed to characterize implantation-associated genes in these two species. Results: We identified a total of 518 differentially expressed genes in mouse uterus during implantation, of which 253 genes were up-regulated and 265 genes were down-regulated at the implantation sites compared with the inter-implantation sites. In rat uterus, there were 374 differentially expressed genes, of which 284 genes were up-regulated and 90 genes were down-regulated. A cross-species comparison revealed that 92 up-regulated genes and 20 down-regulated genes were shared. The differences and similarities between mice and rats were investigated further at the gene ontology, pathway, network, and causal transcription factor levels. Additionally, we found that embryo implantation might have evolved through the recruitment of ancient genes into uterine expression. The evolutionary rates of the differentially expressed genes in mouse and rat uterus were significantly lower than those of the non-changed genes, indicating that implantation-related genes are evolutionary conserved due to high selection pressure. Conclusion: Our study provides insights into the molecular mechanisms involved in the evolution of embryo implantation.

The Role of MicroRNAs in Mammalian Fertility: From Gametogenesis to Embryo Implantation

“…Indeed, the "cross-talk" between the embryo and the uterus involves the expression of a diverse array of genes. For instance, differential expression of 518 and 374 genes between implantation sites and inter-implantation sites in mouse and rat uterus, respectively suggests the induction or repression of arrays of endometrial genes at the site of embryo attachment [133].…”

Cell–Cell Communication at the Embryo Implantation Site of Mouse Uterus Revealed by Single-Cell Analysis

“…By using uterus-specific gene knockout mice, a number of genes have been proven to be required for embryo implantation [ 5 ]. Alternatively, several studies have analyzed global gene expression changes between implantation sites and inter-implantation sites of mouse uterus using high-throughput transcriptomic approaches, providing a useful candidate gene list for further study of embryo implantation [ 6 , 7 , 8 ]. The limitation of these studies is that the whole uterus is used.…”

The endometrial transcriptome transition preceding receptivity to embryo implantation in mice

“…Despite studies describing several key processes and factors involved in embryo implantation in mice, a comprehensive understanding of the transcriptional changes that occur in the uterus in order to acquire receptivity to embryo implantation, and the upstream signals that drive these changes, is lacking. Previous studies have focused on comparisons of uterine tissue compartments, for example comparing implantation sites and inter-implantation sites [ 25 ] at time points day 3.5 post-coitum (pc) (pre-implantation), day 4.5 pc (the time of implantation) and day 5.5 or 6.5 pc (post-implantation) [ 26 – 29 ], using microarray gene expression analysis or quantitative polymerase chain reactions (qPCRs) [ 29 , 30 ]. While these comparisons focus on the molecular changes at or around the time of implantation, they do not provide information on the overarching molecular mechanisms by which the peri-implantation state evolves from its earlier peri-ovulatory state.…”