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Natural killer cell subsets in endometrial fluid: a pilot study of their association with the endometrial cycle and reproductive parameters

  • Reproductive physiology and disease
  • Published:
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Abstract

Purpose

To investigate if there are natural killer (NK) cells in endometrial fluid (EF) and their relationship with the endometrial cycle and reproductive parameters.

Methods

The population under study consisted of 43 women aged 18–40 undergoing infertility workup at our University Hospital in 2021–2022.

The EF samples were obtained at the first visit to our unit, on occasion of the mock embryo transfer. The day of the cycle was considered only in cycles of 27–29 days.

An immunophenotype study of NK in EF was performed by flow cytometry analysis. In a subgroup of women, on the same day, NK was studied in EF and peripheral blood.

Results

Our study is the first to evidence NK cells in EF. None of the NK cells observed corresponded to a mature peripheral blood NK cell population (stages 4–5), and neither endometrial nor decidual uNK cells were detected. Nevertheless, we found 2 patient groups with an NK cell subset with a higher expression of CD16+, which could belong to an intermediate or transient stage between the uNK and pbNK NK cell population in the EF. We found that CD16 was significantly increased in the mid-late luteal phase and its correlation with the day of the cycle. The NK immunophenotype was different in EF and peripheral blood.

Conclusion

We described a new component of the EF, the NK cells, whose CD16 activity is closely correlated with the day of the cycle. These cells could play a role in implantation/implantation failure.

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Acknowledgements

We apologize to our colleagues whose work was not cited due to space limitations. We would like to thank the Basque Biobank for Research (Biobanco Vasco) for the collection of the samples.

Funding

This work was supported by grants 2020111058, 2020333032, 2019111068, and 2022111067 from the Health Department of the Basque Government; Merck-Salud Foundation (FSALUD17/004), Inocente, Inocente Foundation (FII22/001) and Jesus de Gangoiti Barrera Foundation, and the Grant for Fertility Innovation (GFI, 2011) from Merck (Darmstadt, Germany).

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Author notes

  1. Lara Herrera, Myriam Martin-Inaraja, Cristina Eguizabal and Roberto Matorras contributed equally to this work.

Authors and Affiliations

  1. Cell Therapy, Stem Cells and Tissues Group, Basque Centre for Blood Transfusion and Human Tissues, 48960, Galdakao, Spain

    Lara Herrera, Myriam Martin-Inaraja & Cristina Eguizabal

  2. Cell Therapy, Stem Cells and Tissues Group, Biocruces Bizkaia Health Research Institute, 48903, Barakaldo, Spain

    Lara Herrera, Myriam Martin-Inaraja & Cristina Eguizabal

  3. Human Reproduction Unit, Department of Obstetrics and Gynecology, Cruces University Hospital, Barakaldo, Spain

    Ainara Bengoetxea & Roberto Matorras

  4. Biocruces Bizkaia Health Research Institute, Plaza de Cruces s/n, 48903, Barakaldo, Spain

    Ainara Bengoetxea, Alberto Vendrell, Silvia Pérez-Fernández & Roberto Matorras

  5. Department of Medical-Surgical Specialties, Basque Country University, Lejona, Spain

    Roberto Matorras

  6. Instituto Valenciano de Infertilidad – IVI Bilbao, IVIRMA, Lejona, Spain

    Roberto Matorras

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  1. Lara Herrera
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Correspondence to Alberto Vendrell.

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All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964 and its later amendments. The study was approved by our Institutional Ethical and Investigation Board (CEIC code E21/63).

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Herrera, L., Martin-Inaraja, M., Bengoetxea, A. et al. Natural killer cell subsets in endometrial fluid: a pilot study of their association with the endometrial cycle and reproductive parameters. J Assist Reprod Genet 40, 2241–2250 (2023). https://doi.org/10.1007/s10815-023-02862-4

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