Genome-wide Profiling Of Microrna And Mrna Expression Patterns Of Endometrium On The Day Of Oocyte-retrieval After Controlled Ovarian Stimulation

Objective: During in vitro fertilization and embryo transfer(IVF-ET),controlled ovarian stimulation(COS)exposes the endometrium to supra-physiological levels of estrogen and progesterone,which may affect endometrial development and receptivity.This study aims to establish the differential micro RNA(miRNA)and mRNA expression profiles of endometrial on the day of oocyte-retrieval between COS cycle and natural cycle(NC).And to demonstrate the role of dysregulated miRNAs and mRNAs,as well as their network in endometrium induced by COS.Material and methods: In this study,endometrial biopsy samples on the day of oocyteretrieval were collected from 4 women both in COS cycle and NC,of which micro RNA(miRNA)and mRNA expression profiles were estabilished.Clinical information of each patient was collected and compared between the two groups.Differential miRNAs and mRNAs were screened according to p value<=0.05 and log2(fold-change)>=1 or log2(fold-change)<=-1,and were validated by qRT-PCR.The functional and signaling pathways of dysregulated mRNA were analyzed by GO and KEGG enrichment analysis.Target Scan,mi RDB,mi RTar Base,and mi Randa databases were included to predict target genes of miRNAs.Target genes predicted by at least two databases were selected for miRNA-mRNA regulatory network construction.Results:1.A total of 3218 differentially expressed mRNAs(including 1482 up-regulated and 1736 down-regulated)and 30 differentially expressed miRNAs(including 13 upregulated and 17 down-regulated)were obtained.2.The differential expression of mi R-424-5p,mi R-503-5p,SCL38A1,SLC7A2,GABRP,PNP,LIF have been validated by qRT-PCR.3.Enrichment of functions and signal pathways of 3218 differentially expressed mRNAs were carried by GO and KEGG enrichment analysis.The top 5 enrichment pathways of KEGG analysis include mineral absorption,protein digestion and absorption,ECM-receptor interaction,cell cycle,and calcium signal pathway.4.Among the desregulated mRNAs,target genes of differential miRNAs were predicted,and a miRNA-mRNA regulatory network was constructed.Conclusions:1.Our study demonstrates the differential miRNA and mRNA expression profiles of endometrium on the day of oocyte-retrieval between COS cycle and NC.2.And further bioinformatics analysis indicates the role of the dysregulated miRNAs,mRNAs as well as their network of endometrium induced by COS.