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Transcriptome sequencing of endometrium revealed alterations in mRNAs and lncRNAs after ovarian stimulation

  • Assisted Reproduction Technologies
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Abstract

Research question

Using RNA-sequencing analysis, we investigated the relationship between ovarian stimulation and endometrial transcriptome profiles during the window of implantation (WOI) to identify candidate predictive factors for the WOI and to optimize timing for embryo transfer.

Methods

Twelve women with normal basal hormone levels and regular ovulation were randomly assigned into three groups based on sampling time: late-proliferate phase (P group), and receptive phase in natural cycles (LH+7, N group) and stimulated cycles (hCG+7, S group). Transcriptome profiles of mRNAs and long non-coding RNAs (lncRNAs) were then compared among the three groups. Validation was performed using real-time qPCR.

Results

Comparison of transcriptome profiles between the natural and stimulated endometrium revealed 173 differentially expressed genes (DEGs), with a > 2-fold change (FC) and p < 0.05, under the influence of supraphysiological estradiol (E2) induced by ovarian stimulation. By clustering and KEGG pathway analysis, molecules and pathways associated with endometrial receptivity were identified. Of the 39 DEGs common to the three groups, eight genes were validated using real-time PCR. ESR1, MMP10, and HPSE were previously reported to be associated with endometrial receptivity. In addition, three novel genes (IL13RA2, ZCCHC12, SRARP) and two lncRNAs (LINC01060, LINC01104) were new potential endometrial receptivity-related markers.

Conclusion

Using mRNA and lncRNA sequencing, we found that supraphysiological E2 levels from ovarian stimulation had a marked impact upon endometrial transcriptome profiles and may result in a shift of the WOI. The precise mechanisms underlying the supraphysiological hormone-induced shift of the WOI require further research.

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ChiCTR180001453

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Authors and Affiliations

  1. Medical Center for Human Reproduction, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China

    Lingxiu Li, Peng Wang, Shan Liu, Xueyan Bai & Yuan Li

  2. Beijing NeoAntigen Biotechnology Co. Ltd, Beijing, China

    Binbin Zou

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  1. Lingxiu Li
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Li, L., Wang, P., Liu, S. et al. Transcriptome sequencing of endometrium revealed alterations in mRNAs and lncRNAs after ovarian stimulation. J Assist Reprod Genet 37, 21–32 (2020). https://doi.org/10.1007/s10815-019-01616-5

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