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Association between endometrial senescent cells and immune cells in women with repeated implantation failure

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

Abstract

Purpose

The aim of this study was to compare women with recurrent implantation failure (RIF) and control group in terms of the associations between p16-positive senescent cells and certain types of immune cells in human endometrium during the mid-luteal phase

Methods

Immunohistochemical staining was performed in 116 endometrial biopsies taken from 57 women presenting RIF, and control group of 59 women who became pregnant after the first intracytoplasmic sperm injection. Endometrial tissue sections were stained immunohistochemically for p16 (Senescent cells), CD4 (T-helpers), CD8 (T-killers), CD14 (Monocytes), CD68 (Macrophages), CD56 (Natural killers), and CD79α (B-cells). The percentage of positively stained cells for each marker was calculated by HALO image analysis software. The quantity and the relationship between senescent cells and immune cells were assessed and compared between the two groups.

Results

The correlation coefficient was highest between senescent cells and CD4+ cells and was lowest between senescent cells and CD14+ cells in RIF women, similarly to the control group. However, most of the observed correlations among senescent and immune cells weaken notably or disappear in the RIF group. When comparing senescent cell-to-immune cell quantitative ratios, only p16+/CD4+ cell ratio was significantly higher in RIF women as compared with patients from the control group.

Conclusion

Our study indicates that the quantity of senescent cells in human endometrium during the mid-luteal phase has the strongest association with the amount of T helpers. Moreover, the specificity of this association might have an important impact on the occurrence of RIF.

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Acknowledgements

The authors thank Yoana Baleva for proofreading and comments on the manuscript.

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Authors and Affiliations

  1. Research Department, Nadezhda Women’s Health Hospital, Sofia, Bulgaria

    D. Parvanov, R. Ganeva, K. Arsov, I. Decheva, M. Handzhiyska, M. Ruseva & N. Vidolova

  2. Centre for Endocrinology and Reproductive Medicine, Rome, Italy

    F. Scarpellini

  3. Pathology Department, Nadezhda Women’s Health Hospital, Sofia, Bulgaria

    D. Metodiev

  4. Obsterics and Gynecology Department, Nadezhda Women’s Health Hospital, Sofia, Bulgaria

    G. Stamenov

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  1. D. Parvanov
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Contributions

All authors qualify for authorship by contributing substantially to this article. DP, RG, FS and GS developed the original concept and design of the study. DP, RG, KA, ID, MR, MK, and NV collected the data, DP, KA, and ID performed the statistical analysis and DP, RG, FS, DM and GS provided input to the interpretation of the data. All authors have contributed to critical discussion, reviewed the final version of the article, and approved it for publication.

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Correspondence to D. Parvanov.

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This experimental study and the collection of endometrial tissue were approved by the hospital’s Ethics committee and were carried out according to the principles in the Declaration of Helsinki. Written informed consent was obtained from all recruited participants.

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There are no competing interests related to this study.

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Parvanov, D., Ganeva, R., Arsov, K. et al. Association between endometrial senescent cells and immune cells in women with repeated implantation failure. J Assist Reprod Genet 40, 1631–1638 (2023). https://doi.org/10.1007/s10815-023-02821-z

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