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miR-181d-5p, which is upregulated in fetal growth restriction placentas, inhibits trophoblast fusion via CREBRF

  • Reproductive physiology and disease
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

A Correction to this article was published on 10 November 2023

A Correction to this article was published on 19 October 2023

This article has been updated

Abstract

Purpose

Fetal growth restriction (FGR) is a common complication characterized by impaired placental function and unfavorable pregnancy outcomes. This study aims to elucidate the expression pattern of miR-181d-5p in FGR placentas and explore its effects on trophoblast fusion.

Methods

The expression pattern of miR-181d-5p in human FGR placentas were evaluated using qRT-PCR. Western blot, qRT-PCR, and Immunofluorescence analysis were performed in a Forskolin (FSK)-induced BeWo cell fusion model following the transfection of miR-181d-5p mimic or inhibitor. Potential target genes for miR-181d-5p were identified by screening miRNA databases. The interaction between miR-181d-5p and Luman/CREB3 Recruitment Factor (CREBRF) was determined through a luciferase assay. Moreover, the effect of CREBRF on BeWo cell fusion was examined under hypoxic conditions.

Results

Aberrant up-regulation of miR-181d-5p and altered expression of trophoblast fusion makers, including glial cell missing 1 (GCM1), Syncytin1 (Syn1), and E-cadherin (ECAD), were found in human FGR placentas. A down-regulation of miR-181d-5p expression was observed in the FSK-induced BeWo cell fusion model. Transfection of the miR-181d-5p mimic resulted in the inhibition of BeWo cell fusion, characterized by a down-regulation of GCM1 and Syn1, accompanied by an up-regulation of ECAD. Conversely, the miR-181d-5p inhibitor promoted BeWo cell fusion. Furthermore, miR-181d-5p exhibited negative regulation of CREBRF, which was significantly down-regulated in the hypoxia-induced BeWo cell model. The overexpression of CREBRF was effectively ameliorated the impaired BeWo cell fusion induced by hypoxia.

Conclusions

Our study demonstrated that miR-181d-5p, which is elevated in FGR placenta, inhibited the BeWo cell fusion through negatively regulating the expression of CREBRF.

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Data availability

All data in this study are included in this manuscript.

Change history

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Acknowledgements

Gratefully acknowledge all study participants for their contributions.

Funding

This work was partly funded by the National Natural Science Foundation of China, (Grant no. 82171664, 81801458) and the Natural Science foundation of Chongqing, China, (Grant no. CSTB2022NSCQ-LZX0062, cstc2021jcyj-msxmX0236).

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Women and Children’s Hospital of Chongqing Medical University, No.120 Longshan Road, Yubei District, Chongqing, 401147, China

    Zhi-Hong Wu & Yu-Bin Ding

  2. Joint International Research Laboratory of Reproduction and Development of the Ministry of Education of China, Chongqing Medical University, Chongqing, China

    Zhi-Hong Wu, Fang-Fang Li, Ling-Ling Ruan, Shuang Zhang, Zhuo-Hang Li, Antonia Otoo, Jing Tang, Tai-Hang Liu & Yu-Bin Ding

  3. Department of Pharmacology, the School of Traditional Chinese Medicine, Chongqing Medical University, Chongqing, China

    Li-Juan Fu

  4. Academician Workstation, Changsha Medical University, Changsha, China

    Li-Juan Fu

  5. Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases, Chongqing Medical University, Chongqing, China

    Qian Feng

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  1. Zhi-Hong Wu
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Contributions

Tai-Hang Liu and Li-Juan Fu conceived and designed the study. Zhi-Hong Wu conducted most of the experiments and wrote the manuscript. Fang-Fang Li and Ling-Ling Ruan contributed to data analysis. Qian Feng, Shuang Zhang, Zhuo-Hang Li, Antonia Otoo, and Jing Tang revised the manuscript. Yu-Bin Ding designed, coordinated, and revised the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Li-Juan Fu, Tai-Hang Liu or Yu-Bin Ding.

Ethics declarations

Ethics approval and consent to participate

This project was approved by the Biomedical Research Ethics Committee of Chongqing Medical University. Informed consent was obtained from pregnant women that participated in this study.

Consent for publication

Written consent has been obtained from each patient or subject after full explanation of the purpose and nature of all procedures used.

Competing interests

There is no conflict of interest that could have appeared to influence the work reported in this paper.

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The original online version of this article was revised: The author realized that the information details in the text line under Materials and Method are incorrect.

Incorrect Information: anti-CREBRF (1:250, Santa Cruz Biotechnology, CA, USA, sc-393012)

Corrected Information: anti-CREBRF (1:1000, Thermo Fisher, MA, USA, PA5-68552)

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Wu, ZH., Li, FF., Ruan, LL. et al. miR-181d-5p, which is upregulated in fetal growth restriction placentas, inhibits trophoblast fusion via CREBRF. J Assist Reprod Genet 40, 2725–2737 (2023). https://doi.org/10.1007/s10815-023-02917-6

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