Long non-coding RNAs in human early embryonic development and their potential in ART

Abstract

BACKGROUND: Human long non-coding RNAs (lncRNAs) are an emerging category of transcripts with increasingly documented functional roles during development. LncRNAs and roles during human early embryo development have recently begun to be unravelled. OBJECTIVE AND RATIONALE: This review summarizes the most recent knowledge on lncRNAs and focuses on their expression patterns and role during early human embryo development and in pluripotent stem cells (PSCs). Public mRNA sequencing (mRNA-seq) data were used to illustrate these expression signatures. SEARCH METHODS: The PubMed and EMBASE databases were first interrogated using specific terms, such as 'lncRNAs', to get an extensive overview on lncRNAs up to February 2016, and then using 'human lncRNAs' and 'embryo', 'development', or 'PSCs' to focus on lncRNAs involved in human embryo development or in PSC. Recently published RNA-seq data from human oocytes and pre-implantation embryos (including single-cell data), PSC and a panel of normal and malignant adult tissues were used to describe the specific expression patterns of some lncRNAs in early human embryos. OUTCOMES: The existence and the crucial role of lncRNAs in many important biological phenomena in each branch of the life tree are now well documented. The number of identified lncRNAs is rapidly increasing and has already outnumbered that of protein-coding genes. Unlike small non-coding RNAs, a variety of mechanisms of action have been proposed for lncRNAs. The functional role of lncRNAs has been demonstrated in many biological and developmental processes, including cell pluripotency induction, X-inactivation or gene imprinting. Analysis of RNA-seq data highlights that lncRNA abundance changes significantly during human early embryonic development. This suggests that lncRNAs could represent candidate biomarkers for developing non-invasive tests for oocyte or embryo quality. Finally, some of these lncRNAs are also expressed in human cancer tissues, suggesting that reactivation of an embryonic lncRNA program may contribute to human malignancies. WIDER IMPLICATIONS: LncRNAs are emerging potential key players in gene expression regulation. Analysis of RNA-seq data from human pre-implantation embryos identified lncRNA signatures that are specific to this critical step. We anticipate that further studies will show that these new transcripts are major regulators of embryo development. These findings might also be used to develop new tests/ treatments for improving the pregnancy success rate in IVF procedures or for regenerative medicine applications involving PSC.