Abstract
Recurrent implantation failure (RIF) is a challenge in the field of reproductive medicine, but mechanisms for its occurrence remain still unclear. Long non-coding RNAs (lncRNAs) have been found to play a vital role in many different diseases. In recent years, the differentially expressed lncRNAs have been reported in endometrial tissues. Here, we profiled dysregulated lncRNAs and mRNAs in the endometrial tissues of RIF patients and performed correlation analysis. We found that LINC02190 was upregulated in RIF endometrium and was bound to the integrin αD (ITGAD) mRNA promoter. Immunofluorescence assays were used to detect the location of ITGAD in the Ishikawa cell line and patients’ endometrial biopsies. Overexpressed LINC02190 could decrease the expression of ITGAD and the adhesion rate of Ishikawa and JAR cells. Knockdown of the expression of LINC02190 significantly increased the ITGAD level, as well as the adhesion rate of Ishikawa and JAR cells. Furthermore, we demonstrated that the 150–250 bps of LINC02190 were the cis-elements involved in the regulation of ITGAD promoter activities. In conclusion, the results demonstrated that LINC02190 plays an important role in the occurrence of RIF, and the molecular mechanism may be associated with the embryo–endometrial attachment mediated by ITGAD. This study emphasizes the importance of lncRNAs in the occurrence of RIF and provides a potential new biomarker for diagnosis and therapies.
Highlights
With the rapid development of assisted reproductive technologies (ART), in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) has been widely applied to infertile couples
Recent studies have found an imbalance in the proportion of T helper cells (Liang et al 2015), abnormal expression of cytokines (Thouas et al 2015, Ledee et al 2016), integrins (Coughlan et al 2013), miRNA (Rekker et al 2018), and long ncRNAs (Fan et al 2017, Feng et al 2018) in endometrium or serum are all associated with recurrent implantation failure (RIF) incidence
The results showed that LINC02190 was upregulated in the RIF group, while ITGAD mRNA was downregulated, which was consistent with the LncRNA microarray analysis results (Fig. 4A)
Summary
With the rapid development of assisted reproductive technologies (ART), in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) has been widely applied to infertile couples. ART has improved the pregnancy outcome of infertile females to a certain extent, females with recurrent implantation failure (RIF) still struggle to achieve a favorable clinical pregnancy after multiple embryo transfers. Without accepted formal definition at present, Polanski suggested that RIF could be defined as a failure to achieve embryo implantation after two or more consecutive cycles of IVF/ICSI-ET or frozen-thawed embryo transfer (FET) cycles, where the cumulative number of transferred embryos was no less than four high-quality cleavage-stage embryos or no less than two for blastocysts (Polanski et al 2014). Endometrial receptivity, embryo quality, and the synchronous development of the embryo and endometrium are three essential factors associated with RIF (Koot et al 2012). Recent studies have found an imbalance in the proportion of T helper cells (Liang et al 2015), abnormal expression of cytokines (Thouas et al 2015, Ledee et al 2016), integrins (Coughlan et al 2013), miRNA (Rekker et al 2018), and long ncRNAs (lncRNAs) (Fan et al 2017, Feng et al 2018) in endometrium or serum are all associated with RIF incidence
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