The Low Endometrial Expression of Long Non-Coding RNA NORAD Is Associated with Recurrent Pregnancy Losses and Unexplained Infertility.

ABSTRACT

Objective: Unexplained infertility (UIF) or recurrent pregnancy loss (RPL) affects 10%-15% of couples in their reproductive years and is multifactorial and not completely elucidated. In this study, we attempt to determine the endometrial expression pattern of non-coding RNA activated by DNA damage (NORAD) in women with UIF and RPL, as well as its clinical significance. Methods: The microarray dataset GSE165004 was used to identify differentially expressed RNAs in the endometrial samples between women with RPL and fertile women and between women with UIF and fertile women. A total of 142 women were included in this retrospective analysis, including 32 women with UIF, 48 women with RPL, and 62 fertile women. The relative expression level of NORAD in the endometrial tissues was quantified by qRT-PCR. Results: NORAD stood out as an only overlapped lncRNA among differentially expressed RNAs in the endometrial samples between RPL and fertile women and between UIF and fertile women. It was showed that the endometrial tissues of UIF and RPL both were demonstrated with lower relative expression levels of NORAD (UIF 2.09 ± 0.68; RPL 1.98 ± 0.65) than the endometrial tissues of normal fertility (4.32 ± 1.04) (P < 0.001). Pearson correlation analysis demonstrated that the serum level of E2 was negatively correlated with the relative expression level of NORAD in the endometrial tissues of UIF (r = -0.630) and RPL (r = -0.696). Results of ROC curves showed that the endometrial expression of NORAD could be used to differentiate RPL and UIF with an AUC of 0.977 (95% CI 0.956-0.999) and 0.970 (95% CI 0.941-0.998), sensitivity of 0.873 and 0.955, and specificity of 0.845 and 0.948, respectively. Conclusion: The findings obtained from the study showed that the low endometrial expression of NORAD was linked to fertility-related problems, such as UIF and RPL.