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S100A8 and S100A9 are associated with endometrial shedding during menstruation

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Abstract

Matrix metalloproteinases (MMPs) and their major source, endometrial stromal cells (ESCs), play important roles in menstruation. However, other mechanisms in endometrial shedding may be unexplored. This study focused on four proteins: S100A8 and S100A9 (alarmins) are binding partners and induce MMPs, MMP-3 cycle-dependently plays a key role in the proteolytic cascade, and CD147, which has S100A9 as its ligand, induces MMPs. Immunostaining for these proteins was performed on 118 resected specimens. The percentage and location of each positive reaction in ESCs were measured and compared using Image J. The influence of leukocytes on S100A8 or S100A9 immunopositivity was also examined. From the premenstrual phase, S100A8 and MMP-3 began to have overlapping expressions in ESCs of the superficial layer, and ESC detachment was found within these sites. S100A9 was expressed from the late secretory phase and CD147 already from earlier. Later, the expression sites of S100A9 and CD147 included those of S100A8. Before menstruation, S100A8 or S100A9 expression was not affected by leukocytes. These results suggest that the local formation of S100A8/S100A9 complex, which occurs specifically in ESCs upon progesterone withdrawal, induces the local expression of MMP-3 and serves as a switch to the lysis phase.

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Acknowledgements

The authors would like to thank Enago (http://www.enago.jp) for the English language review.

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All authors were involved in the preparation of this manuscript. KA designed the study, analyzed all pathological data, and wrote the initial draft of the manuscript. AK, TI, AS, and JS contributed to the analysis and interpretation of immunohistochemical data. KA and AS contributed to the analysis and interpretation of clinical data. All authors read and approved the final version of the manuscript.

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Correspondence to Kazumori Arai.

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This case report was approved by the Ethics Committee of Shizuoka General Hospital (Approval no. SGH IRB#2018091/3).

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Arai, K., Kubota, A., Iwasaki, T. et al. S100A8 and S100A9 are associated with endometrial shedding during menstruation. Med Mol Morphol 56, 194–205 (2023). https://doi.org/10.1007/s00795-023-00355-y

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