Identification of serum small non-coding RNA as biomarkers for endometrial receptivity

Background: Current endometrial receptivity analysis is invasive, preventing embryo transfer during the biopsy cycle. This study aims to screen serum sncRNAs as non-invasive biomarkers for ERA tests.

Methods: The study included 12 infertile patients undergoing IVF-ET and ERA, whose serum samples were collected for high-energy sequencing technology to detect sncRNA expression profiles. We overexpressed and knocked down tsRNA-35:73-Asp-GTC-1 in the decidualized Immortalized Human Eutopic Endometrial Stromal Cells (HESC) model cultured in vitro to further investigate the its effect on decidualization. The predicted tsRNA-35:73-Asp-GTC-1 target gene was verified by PCR analysis.

Results: We screened 286 differentially expressed tsRNAs, 46 miRNAs, and 106 piRNAs. KEGG analysis indicated that differentially expressed tsRNAs were associated with pathways such as 'Calcium signaling pathway,' 'Sphingolipid signaling pathway,' etc. The results of RT-qPCR validation showed that the trends of four significantly differentially expressed tsRNAs in serum and endometrium were consistent with sequencing results. ROC curves demonstrated that these four tsRNAs have good predictive value for endometrial receptivity. Overexpression of tsRNA-35:73-Asp-GTC-1 affected the morphology of decidualized cells, and the decidualization indicators also showed a decreasing trend. While knocking down tsRNA-35:73-Asp-GTC-1 had the opposite effect. The RT-qPCR results showed that tsRNA-35:73-Asp-GTC-1 was associated with the Wnt3 target gene.

Conclusion: Serum sncRNA analysis shows potential for studying the molecular mechanisms of endometrial receptivity. Four serum tsRNAs can serve as novel biomarkers for non-invasive endometrial receptivity detection. TsRNA-35:73-Asp-GTC-1 may further regulate endometrial receptivity by targeting Wnt3.