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Loss of Expressions of Dusp6, Sprouty4, and Sef, Negative Regulators of FGF2/ERK1/2 Signaling, in the Endometrium of Women With Adenomyosis

Dual-specificity phosphatase 6 (Dusp6), Sprouty4, and similar expression to FGF (Sef) are negative modulators of FGF2/ERK1/2 signaling. The objective of the study was to evaluate the expressions of Dusp6, Sprouty4, and Sef in eutopic endometria of patients with adenomyosis. Endometria from 30 women with adenomyosis and 29 women without adenomyosis were used in this study. The expressions of Dusp6, Sprouty4, and Sef were investigated by immunohistochemical analysis. We found that Dusp6, Sprouty4, and Sef expressions were present in endometrial epithelial cells of normal endometria and eutopic endometria of adenomyosis. Weak immunostainings were noted in stromal cells in both endometria. No cyclical change was noted either in normal endometria or in eutopic endometria of adenomyosis during menstrual cycle. By immunohistochemical analysis, we found that eutopic endometria of adenomyosis showed significantly decreased Dusp6, Sprouty4, and Sef expressions compared with normal endometria. By in situ hybridization analysis, we found that the mRNA expressions of Dusp6, Sprouty4, and Sef were downregulated in eutopic endometria of adenomyosis compared with normal endometria. We conclude that downregulation of Dusp6, Sprouty4, and Sef—negative modulators of FGF2/ERK1/2 signaling—was present in eutopic endometria of adenomyosis, which may play critical roles in the development of adenomyosis.