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MiRNAs secreted by human blastocysts could be potential gene expression regulators during implantation

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Abstract

Background

Micro RNAs (miRNAs) are small non-coding RNAs known as essential regulators of cell–cell communication. Recent studies have revealed that miRNAs are secreted by a blastocyst in culture media. We hypothesized that endometrial epithelial cells take up embryo-derived miRNAs as well as other soluble factors and regulate their receptivity-related gene expression.

Methods and results

Blastocyst culture media (BCM) were collected from the individually cultured embryos, while human endometrial epithelial cells (HEECs) were collected from healthy fertile volunteers. To evaluate the effect of BCM on the endometrial receptivity gene expression, HEECs were co-cultured with implanted BCM, non-implanted BCM, and a control culture medium. After determining altered gene expression in the HEECs, the miRNAs-related genes through bioinformatics databases were identified and evaluated in the BCM. Co-culture of primary HEECs with BCM significantly stimulated the expression levels of VEGFA, HBEGF, HOXA10, and LIF in the implanted group compared with non-implanted and control groups. The fold changes of miR-195 significantly diminished in the implanted BCM group compared with the non-implanted BCM group. Reduced fold changes of miR‐29b, 145 and increased miR-223 were also observed in the implanted BCM group compared with the non-implanted ones.

Conclusion

miRNAs could function as potential gene expression regulators during implantation. These molecules are secreted by human blastocyst, taken up by endometrial epithelial cells, and cause a change in the endometrial function. We found that BCMs can be effective in implantation process by stimulating related receptivity gene expression.

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Data availability

All data generated or analyzed during this study are included in this published article.

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Acknowledgements

The authors would like to thank the Shahid Akbarabadi Clinical Research Development Unit (ShACRDU), Iran University of Medical Sciences, Tehran, Iran for cooperating throughout the study. This study was financed by Iran University of Medical Sciences (Grant No. 97-01-208-33115).

Funding

This study was financed by Iran University of Medical Sciences (Grant No. 33115).

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Authors and Affiliations

  1. Department of Anatomy, School of Medicine, Iran University of Medical Sciences, Tehran, 1168743514, Iran

    Sadegh Eivazi, Fatemeh Tanhaye Kalate Sabz, Sadegh Amiri, Zahra Zandieh, Mehrdad Bakhtiyari, Fereshteh Mehraein & Fatemehsadat Amjadi

  2. Shahid Akbar Abadi Clinical Research Development Unit (SHACRDU), School of Medicine, Iran University of Medical Sciences (IUMS), Tehran, Iran

    Zahra Zandieh, Mandana Rashidi & Fatemehsadat Amjadi

  3. Department of Endocrinology and Female Infertility, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran

    Reza Aflatoonian

  4. Department of Anatomical Sciences and Pathology, School of Medicine, North Khorasan University of Medical Sciences, bojnurd, Iran

    Fatemeh Tanhaye Kalate Sabz

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  1. Sadegh Eivazi
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Supplementary Information

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Supplementary file1 (TIF 1168.1 kb)—Supplementary Fig. 1 Transferred blastocysts in 5th day.

11033_2022_8121_MOESM2_ESM.tif

Supplementary file2 (TIF 832.5 kb)—Supplementary Fig. 2 Primary endometrial glandular epithelium cell culture. Representative endometrial glandular epithelium at (A) ×100, (B) ×100, (C) ×200 and (D) ×200 magnification. Black arrows indicate glandular epithelium cells.

11033_2022_8121_MOESM3_ESM.tif

Supplementary file3 (TIF 171.6 kb)—Supplementary Fig. 3 Endometrial cell purity. Purified populations of endometrial epithelial cells were stained for the intracellular epithelial and mesenchymal markers cytokeratin and vimentin, respectively. Flow cytometry histograms present data in blue for cells stained with vimentin and cytokeratin, and in red for the cognate isotype control.

11033_2022_8121_MOESM4_ESM.tif

Supplementary file4 (TIF 53.2 kb)—Supplementary Fig. 4 Target genes and related microRNAs were selected according to the miRTargetLink 2.0.

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Eivazi, S., Tanhaye Kalate Sabz, F., Amiri, S. et al. MiRNAs secreted by human blastocysts could be potential gene expression regulators during implantation. Mol Biol Rep 50, 1375–1383 (2023). https://doi.org/10.1007/s11033-022-08121-6

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