Regulatory Mechanism of Human Endometrial Stromal Cell Decidualization by Ergothioneine

Namika Yoshida, Hiromi Murata, Kazuki Ide, Konomi Ide, Marika Tanaka, Minoru Tanaka, Kunio Mori, Kurumi Mori, Kensuke Futani, Misa Sawachika, Hidetaka Okada, Susumu Tanaka
In: Nutraceuticals · 2025 · vol. 5(3) , pp. 16 · doi:10.3390/nutraceuticals5030016 · W4411888285
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Abstract

Endometrial stromal cells (EnSCs) undergo decidualization in response to progesterone. Decidualization facilitates spiral artery remodeling, immune tolerance in the endometrium, and fetal cell invasion and placentation—all essential for successful embryo implantation. Therefore, we aimed to investigate whether ergothioneine (EGT) plays a role in reproduction, particularly in decidualization and implantation. In this study, we found that solute carrier family 22 member 4 (SLC22A4), a specific transporter of EGT—a functional food ingredient with strong anti-aging properties—is upregulated in decidualized EnSCs. The effects of EGT were examined using uterine tissues from patients, primary cultured EnSCs, EnSC cell lines, and co-cultures with a fetal cell line. We observed a significant increase in SLC22A4 expression in secretory-phase human uterine tissue, decidualized EnSCs, and EnSC cell lines. We also found that EGT regulates insulin-like growth factor binding protein 1 expression, which promotes placentation. In co-cultures of EnSC and fetal cell lines, EGT upregulated ectonucleoside triphosphate diphosphohydrolase 1 and major histocompatibility complex, class I, G expression in fetal cell lines—both critical for placentation. These findings suggest that EGT is crucial to regulating decidualization and its markers, particularly insulin-like growth factor-binding protein 1, which contributes to placentation.

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