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Analysis of uterine CD49a+ NK cell subsets in menstrual blood reflects endometrial status and association with recurrent spontaneous abortion

Cellular & Molecular Immunology volume 18, pages 1838–1840 (2021)Cite this article

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Maternal uterine immune cells, especially natural killer (NK) cells, are important for successful pregnancy, and an abnormal number or function of uterine NK cells is closely correlated with an impaired endometrial environment and miscarriage. However, there are currently no noninvasive testing methods using reliable indicators that accurately predict uterine changes leading to miscarriage. Here, we confirmed that before implantation, menstrual blood (MB) from healthy donors had 70% CD49a+ tissue-resident NK (trNK) cells, the majority of which were CD49a+Eomes+ NK cells. Importantly, MB from patients with recurrent spontaneous abortion (RSA) had many fewer CD49a+ trNK cells than MB from controls. Analysis of uNK cell populations in MB may better predict an abnormal endometrial environment associated with miscarriage than peripheral blood (PB) analysis. Therefore, we suggest using MB- and CD49a-related markers as a promising noninvasive way to evaluate endometrial status.

Despite advancing knowledge of the importance of the local endometrial environment and the population of uterine natural killer (uNK) cells in successful pregnancy, prenatal testing for endometrial status in individuals with reproductive disorders is not often implemented because this type of testing usually requires invasive techniques, and there are no reliable indicators for measuring uNK cells. Tests to measure the numbers and cytotoxic potential of PB NK cells in women with reproductive failure have been introduced in many clinics, yet their use is not straightforward.1,2,3 For instance, the normal ranges for PBNK cell numbers and activity vary widely, from 5 to 30% of mononuclear cells among people4, and whether PBNK variation reflects uterine events needs to be investigated. MB is a mixture of blood and tissue from the inner lining of the uterus and has been identified as phenotypically distinct from PB.5,6,7 However, it is unknown whether variations in MBNK cells can be used as indicators to predict miscarriage.

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Acknowledgements

This work was supported by the National Key Research & Developmental Program of China (no. 2018YFC1003900 to H.W.) and the National Natural Science Foundation of China (81930037 to H.W.; 31870914, 81922028 to B.F.), and Youth Innovation Promotion Association of Chinese Academy of Sciences (Grant 2019442 to B.F.).

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  1. These authors contributed equally: Xianhong Tong, Min Gao, Xianghui Du.

Authors and Affiliations

  1. The Department of Obstetrics and Gynecology, First Affiliated Hospital of University of Science and Technology of China, University of Science and Technology of China, Hefei, China

    Xianhong Tong, Min Gao, Fangting Lu, Limin Wu, Haiming Wei & Binqing Fu

  2. Anhui Provincial Hospital Affiliated to Anhui Medical University, Hefei, Anhui, China

    Min Gao

  3. Hefei National Laboratory for Physical Sciences at Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China

    Xianghui Du, Haiming Wei & Binqing Fu

  4. Institute of Immunology, University of Science and Technology of China, Hefei, China

    Xianghui Du, Haiming Wei & Binqing Fu

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  1. Xianhong Tong
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  2. Min Gao
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Contributions

X.T. collected tissue samples and information from patients and assisted with data interpretation. M.G. and X.D. performed the experiments and analyzed and interpreted the data. F.L. and L.W. helped to collect tissue samples and information from patients. H.W. provided strategic planning, conceived the project, and interpreted some data. B.F. supervised the project, designed and provided crucial ideas, and assisted with data interpretation. B.F. wrote the manuscript with M.G. and H.W.

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Correspondence to Haiming Wei or Binqing Fu.

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The authors declare no competing interests.

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Tong, X., Gao, M., Du, X. et al. Analysis of uterine CD49a+ NK cell subsets in menstrual blood reflects endometrial status and association with recurrent spontaneous abortion. Cell Mol Immunol 18, 1838–1840 (2021). https://doi.org/10.1038/s41423-021-00687-8

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