Comparative Transcriptomic Study Of Mouse And Rat Uterus At Implantation Sites

Embryo implantation is an essential process for eutherian pregnancy.Although the eventual objective of implantation,to bring the conceptus into contact with uterus,is the same in all mammals,the different animals have shown wide mechanistic variation.The study of these differences and similarities allows us to gain insights into cellular and molecular interactions that occur during implantation.In this study,we used natural implantation models of mice and rats to study the differences and similarities of gene regulation between the two species.The tissue from implantation site and non-implantation site of uterus in mice and rats were dissected and subjected to RNA-seq analysis,respectively.As a result,we identified a total of 518 differentially expressed genes in the mouse implantation site,of which 253 genes were upregulated and 265 were down-regulated compared to non-implantation site.There were 374 differentially expressed genes in the rat implantation site,of which 284 genes were upregulated and 90 were down-regulated compared to non-implantation site.In order to further understand the functions of differentially expressed genes,we performed gene ontology(GO)analysis,KEGG pathway analysis,network analysis and transcription factor binding site analysis,respectively.GO analysis showed that the functions of genes involved in mouse and rat implantation were largely overlapped,e.g.cell metabolism,proliferation and differentiation.Gene network analysis revealed that there were 15 hub genes in the gene-gene interaction network of mouse(Ripk4,Akt1,Top2 a,Pcna,Umps,Plk1,Hspa1 b,Hspa5,Cdc20,Oasl2,Oas2,Rev3 l,Pold1,Cdkn1 b and Ccna2)and 11 hub genes in the gene-gene interaction network of rat(Top2a,Cad,Hsp90aa1,Cdk4,Hist2h3c2,Xpo1,Hspa5,Mad2l1,Fos,Acta2 and Cenpe).There were 2 hub genes(Top2a and Hspa5)shared by both mice and rats.These hub genes represent functionally important genes due to their key positions in the networks and thus deserve further investigation.In the analysis of mouse transcription factors,the binding sites of ETF,ZF5,E2F-1,E2F-4:DP-2,MOVO-B,Sp1 and SREBP-1 were significantly over-represented,while in the analysis of rat transcription factors,the binding sites of ETF,E2F-4:DP-2 and MOVO-B were significantly over-represented.ETF,E2F-4:DP-2 and MOVO-B binding sites were shared by both mice and rats.Furthermore,we evaluated the gene age of differentially expressed genes.We found that embryo implantation might evolved through the recruitment of old genes into uterine expression.Additionally,we observed that the evolutionary rate of differentially expressed genes in mouse and rat uterus was significantly lower than the non-changed genes.This result indicated that implantation-related genes are evolutionary conserved.In summary,this study screened differentially expressed genes in mouse and rat uterine implantation sites.Through the bioinformatics analysis and evolutionary analysis of differentially expressed genes,gene function and gene evolution in mouse and rat implantation are demonstrated.This study is helpful to further understand the molecular mechanisms of embryo implantation.