Abstract
Establishment of the receptive uterus is a crucial step for embryo implantation. In this study, the expression profiles and characterization of long non-coding RNAs (lncRNAs) in pregnant mouse uteri on day 4, day 5 at implantation sites and inter-implantation sites were conducted using RNA-seq. A total of 7,764 putative lncRNA transcripts were identified, including 6,179 known lncRNA transcripts and 1,585 novel lncRNA transcripts. Bioinformatics analysis of the cis and trans lncRNA targets showed that the differentially expressed lncRNAs were mainly involved in tissue remodelling, immune response and metabolism-related processes, indicating that lncRNAs could be involved in the regulation of embryo implantation. We also discovered that differentially expressed lncRNAs might regulate multiple signalling pathways that play an important role in the regulation of embryo implantation. In addition, nine known lncRNAs and four novel lncRNAs were randomly selected and validated by qRT-PCR. The expression of Tug1, Neat1, Gas5, Malat1, H19 and Rmst were significantly regulated in the mouse uterus during the implantation window. Our results are the first to systematically identify lncRNAs in the mouse uterus and provide a catalogue of lncRNAs for further understanding their functions in pregnant mouse uteri during the implantation window.
Highlights
In mammalian reproduction, the establishment of a receptive uterus is an essential step for successful embryo implantation, which only occurs in a spatiotemporally restricted time known as the ‘‘implantation window’’
We discovered that differentially expressed long non-coding RNAs (lncRNAs) might regulate multiple signalling pathways that play an important role in the regulation of embryo implantation
Several studies using genome-wide analysis have revealed many up- and down-regulated protein-coding genes at the implantation and interimplantation sites in whole mouse uterine tissue or luminal epithelium during embryo implantation [26, 27]
Summary
The establishment of a receptive uterus is an essential step for successful embryo implantation, which only occurs in a spatiotemporally restricted time known as the ‘‘implantation window’’. The endometrium becomes receptive to blastocyst implantation on the morning of day 4 of pregnancy (day of plug = D1). Endometrium receptivity lasts for 18-24 h and usually ends by the afternoon of day 5 of pregnancy [1]. In humans, increased implantation failure or early pregnancy loss is observed after implantation occurring beyond the implantation window or at a non-receptive stage [2]. In response to the implanting embryo, the receptive uterus generates numerous factors during implantation, but it is revealed that only a few of them are essential to this process. Obtain a global view and identify novel implantation periodspecific genes is necessary to further understand molecular mechanisms underlying embryo implantation
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