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

  • Lingxiu Li
  • Peng Wang
  • Shan Liu
  • Xueyan Bai
  • Binbin Zou
  • Yuan LiEmail author
Assisted Reproduction Technologies


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.


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.


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.


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.

Registration number



Ovarian stimulation Window of implantation Endometrial receptivity mRNAs lncRNAs 


Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

10815_2019_1616_MOESM1_ESM.rar (2.7 mb)
ESM 1 (RAR 2715 kb)


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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Medical Center for Human Reproduction, Beijing Chao-Yang HospitalCapital Medical UniversityBeijingChina
  2. 2.Beijing NeoAntigen Biotechnology Co. LtdBeijingChina

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