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Increased expression of HMGB1 in the implantation phase endometrium is related to recurrent implantation failure

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Abstract

Background

Impaired endometrial receptivity was the main cause of recurrent implantation failure (RIF); however, its underlying mechanisms had not been elucidated. This study aimed to determine the expression level of high-mobility group box protein 1 (HMGB1) in the endometrium with RIF and its effect on endometrial receptivity.

Methods and results

Genome-wide expression profiling, real-time reverse transcription PCR, immunohistochemical staining, western blot, and in vitro assays were performed in this study. We found that HMGB1 expression was significantly decreased in the implantation phase endometrium in the control group (patients with tubal infertility and successfully achieve conception after the first embryo transfer) (P = 0.006). However, the expression levels of HMGB1 mRNA and protein were significantly upregulated during the implantation phase in endometrial tissues obtained from patients with RIF compared to that in the control group (P = 0.001), consistent with the results of the genome-wide expression profiling. Moreover, in vitro assays showed that increased expression of HMGB1 in human endometrial epithelial cells dramatically displayed a marked deficiency in supporting blastocysts and human embryonic JAR cells adhesion, which mimic the process of embryo adhesion.

Conclusion

These findings strongly indicated that increased HMGB1 levels suppressed the epithelial cell adhesion capability, therefore contributing to impaired endometrial receptivity in patients with recurrent implantation failure, which can be used as a target for the recognition and treatment of recurrent implantation failure in clinical practice.

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Acknowledgements

The authors thank all of the professors at the Institute of State Key Laboratory of Medical Genomics, Shanghai Ruijin Hospital for their help.

Funding

This work was supported by the National Natural Science Foundation of China [Grant Numbers 82071596 and 81701513].

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Author notes

  1. Mi Han and Yi Cao have contributed equally to this work.

Authors and Affiliations

  1. Department of Reproductive Medical Center, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, 197 Ruijin 2nd Road, Shanghai, 200025, China

    Mi Han, Wenjie Zhou, Mingjuan Zhou, Xiaowei Zhou, Dan Zhang, Bufang Xu & Aijun Zhang

  2. Department of Obstetrics and Gynecology, Minhang Hospital, Fudan University, 170 Xin Song Road, Shanghai, 201100, China

    Yi Cao

  3. Shanghai Key Laboratory of Reproductive Medicine, 280 South Chongqing Road, Shanghai, 200025, China

    Aijun Zhang

Authors
  1. Mi Han
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  2. Yi Cao
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  3. Wenjie Zhou
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  4. Mingjuan Zhou
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  5. Xiaowei Zhou
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  6. Dan Zhang
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  7. Bufang Xu
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  8. Aijun Zhang
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Contributions

MH: protocol/project development, data collection or management, data analysis, manuscript writing/editing; YC: data collection or management, data analysis; WZ: conceptualization; MZ: data curation; XZ: data curation; DZ: funding acquisition, resources; BX: writing—review and editing, resources; AZ: writing—review and editing, funding acquisition.

Corresponding authors

Correspondence to Bufang Xu or Aijun Zhang.

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Conflict of interests

The authors declare that they have no conflicts of interest exist.

Ethical approval

The study has been granted by the Institutional Ethics Committee of Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University (2012-57). All patients signed an informed consent form before they were recruited in the study.

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Han, M., Cao, Y., Zhou, W. et al. Increased expression of HMGB1 in the implantation phase endometrium is related to recurrent implantation failure. Mol Biol Rep 49, 1701–1710 (2022). https://doi.org/10.1007/s11033-021-06979-6

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  • DOI: https://doi.org/10.1007/s11033-021-06979-6

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