Genome-wide Identification of Micro-ribonucleic Acids Associated with Human Endometrial Receptivity in Natural and Stimulated Cycles by Deep Sequencing

Objective: To identify microRNAs (miRNAs) associated with endometrial receptivity.

Design: Observational study.

Setting: Medical center.

Patient(s): Healthy, regularly cycling women undergoing IVF treatment.

Intervention(s): Gonadotropin stimulation and endometrial biopsy.

Main Outcome Measure(s): Quantification of miRNA expression profiles by deep sequencing.

Result(s): The miRNA expression profiles in human endometrium on days LH+2 and LH+7 (LH = 0 is the day of the LH surge) in natural cycles as well as on days hCG+4 and hCG+7 (hCG = 0 is the day of hCG injection) in stimulated cycles were determined by deep sequencing. In natural cycles, there were 20 significantly changed miRNAs in human endometrium on LH+7 compared with LH+2. These miRNAs were predicted to target a large set of genes with different functions, including cell cycle, transport, cell adhesion, cell death, and metabolism. In stimulated cycles, 22 miRNAs were significantly dysregulated on hCG+7 in comparison with LH+7, 11 of which exhibited putative estrogen response elements or P response elements in the promoters. Additionally, unsupervised hierarchical clustering analysis demonstrated that the miRNA expression profile on hCG+4 was similar to that on LH+7, suggesting that ovarian stimulation may alter the window of endometrial receptivity.

Conclusion(s): MiRNAs may be novel biomarkers for human endometrial receptivity and may help optimize the protocol for IVF treatment.