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Endometrial extracellular vesicles of recurrent implantation failure patients inhibit the proliferation, migration, and invasion of HTR8/SVneo cells

  • Reproductive Physiology and Disease
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

Endometrial extracellular vesicles are essential in regulating trophoblasts’ function. This study aims to investigate whether endometrial extracellular vesicles (EVs) from recurrent implantation failure (RIF) patients inhibit the proliferation, invasion, and migration of HTR8/SVneo cells.

Methods

Eighteen RIF patients and thirteen fertile women were recruited for endometria collection. Endometrial cells isolated from the endometria were cultured and modulated by hormones, and the conditioned medium was used for EV isolation. EVs secreted by the endometrial cells of RIF patients (RIF-EVs) or fertile women (FER-EVs) were determined by Western blotting, nanoparticle tracking analysis, and transmission electron microscopy. Fluorescence-labeled EVs were used to visualize internalization by HTR8/SVneo cells. RIF-EVs and FER-EVs were co-cultured with HTR8/SVneo cells. Cell Counting Kit-8, transwell invasion, and wound closure assays were performed to determine cellular proliferation, invasion, and migration, respectively, in different treatments.

Results

RIF-EVs and FER-EVs were bilayer membrane vesicles, ranging from 100 to 150 nm in size, that expressed the classic EV markers Alix and CD9. RIF-EVs and FER-EVs were internalized by HTR8/SVneo cells within 2 h. The proliferation rate in the FER-EV group was significantly higher than that in the RIF-EV group at 20 μg/mL. Moreover, the invasion and migration capacity of trophoblast cells were decreased in the RIF-EV group relative to the FER-EV group at 20 μg/mL.

Conclusion

Endometrial EVs from RIF patients inhibited the functions of trophoblasts by decreasing their proliferation, migration, and invasive capacity. Such dysregulations induced by RIF-EVs may provide novel insights for better understanding the pathogenesis of implantation failure.

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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

The current study was supported by grants from the National Natural Science Foundation of China (NSFC 81771582 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, Linshuang Li, Meng Wang, Shike Shui, Haixia Yao, Cong Sui & Hanwang Zhang

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  1. Chang Liu
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Contributions

C.L. designed the experiments. C.L., L.L., H.Y., and S.S. collected the endometrial samples. C.L., S.S., 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.

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Liu, C., Li, L., Wang, M. et al. Endometrial extracellular vesicles of recurrent implantation failure patients inhibit the proliferation, migration, and invasion of HTR8/SVneo cells. J Assist Reprod Genet 38, 825–833 (2021). https://doi.org/10.1007/s10815-021-02093-5

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