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Altered microRNA Profiles of Extracellular Vesicles Secreted by Endometrial Cells from Women with Recurrent Implantation Failure

  • Infertility: Original Article
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Abstract

Recurrent implantation failure (RIF) is characterized by repeated embryo transfers without pregnancy. To date, the etiology of RIF remains poorly understood. Accumulating evidence indicates a beneficial role of endometrial extracellular vesicles (EVs) during the implantation by delivering signaling molecules to embryos, especially miRNAs. However, whether EVs secreted by RIF patients’ endometria have a similar miRNA expression profile of endometrial EVs of fertile women has not been investigated. Therefore, in this study, we compared the miRNA expression profiles between the endometrial EVs of RIF patients (RIF-EVs) and fertile women (FER-EVs). Endometrial tissues from fifteen RIF patients and nine fertile women were collected and digested to cells for culture. Endometrial cells were modulated by estrogen and progesterone to mimic the secretory phase, and the conditioned medium was collected for EV isolation. EVs were determined by western blotting, nanoparticle tracking analysis, and transmission electronic microscopy (TEM). Three pairs of EV samples from two groups were used for miRNA sequencing, and twelve RIF-EV samples and six FER-EV samples were used for validation using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Results showed that a total of 11 miRNAs were differently expressed in the RIF-EVs. Besides, four of the differently expressed miRNAs were validated using qRT-PCR. Target genes of the differently expressed miRNAs were predicted, and the functional analysis was performed. Besides, we proved that the most significantly different miRNA, 6131, inhibited the growth and invasion of HTR8/SVneo cells. Our study suggested that the altered miRNAs in the RIF-EVs might be involved in the pathogenesis of RIF.

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Data Availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Funding

This study was supported by the National Natural Science Foundation of China (NSFC 81771582, NFSC 81901561, and NSFC 81701450).

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Authors and Affiliations

  1. Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue 1095#, Wuhan, 430030, People’s Republic of China

    Chang Liu, Meng Wang, Hanwang Zhang & Cong Sui

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  1. Chang Liu
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  2. Meng Wang
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  4. Cong Sui
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Contributions

C.L. designed the experiments. C.L. collected the endometrial samples. C.L. and M.W. performed the experiments. C.L. wrote the manuscript, which was revised by H.Z. and C.S.

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Correspondence to Hanwang Zhang or Cong Sui.

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This study was approved by the Institutional Review Board of Tongji Hospital (TJ-IRB20190420).

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Liu, C., Wang, M., Zhang, H. et al. Altered microRNA Profiles of Extracellular Vesicles Secreted by Endometrial Cells from Women with Recurrent Implantation Failure. Reprod. Sci. 28, 1945–1955 (2021). https://doi.org/10.1007/s43032-020-00440-y

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