Uterine prostaglandin DP receptor-induced upon implantation contributes to decidualization together with EP4 receptor.

Autor: Sakamoto R; Department of Pharmaceutical Biochemistry, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan., Fujiwara T; Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan., Kawano Y; Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan., Aikawa S; Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan., Inazumi T; Department of Pharmaceutical Biochemistry, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan., Nakayama O; Department of Pharmaceutical Biochemistry, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan., Kawasaki-Shirata Y; Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan., Hashimoto-Iwasaki M; Department of Pharmaceutical Biochemistry, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan., Sugimoto T; Department of Pharmaceutical Biochemistry, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan., Tsuchiya S; Department of Pharmaceutical Biochemistry, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan., Nakao S; Division of Reproductive Engineering, Center for Animal Resources and Development, Kumamoto University, Kumamoto, Japan., Takeo T; Division of Reproductive Engineering, Center for Animal Resources and Development, Kumamoto University, Kumamoto, Japan., Hirota Y; Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan., Sugimoto Y; Department of Pharmaceutical Biochemistry, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan; Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan. Electronic address: ysugi@kumamoto-u.ac.jp.
Jazyk: angličtina
Zdroj: Journal of lipid research [J Lipid Res] 2024 Oct; Vol. 65 (10), pp. 100636. Date of Electronic Publication: 2024 Aug 31.
DOI: 10.1016/j.jlr.2024.100636
Abstrakt: To investigate the yet-unknown roles of prostaglandins (PGs) in the uterus, we analyzed the expression of various PG receptors in the uterus. We found that three types of Gs-coupled PG receptors, DP, EP2, and EP4, were expressed in luminal epithelial cells from the peri-implantation period to late pregnancy. DP expression was also induced in stromal cells within the mesometrial region, whereas EP4 was expressed in stromal cells within the anti-mesometrial region during the peri-implantation period. The timing of DP induction after embryo attachment correlated well with that of cyclooxygenase-2 (COX-2); however, COX-2-expressing stromal cells were located in the vicinity of the embryo, whereas DP-expressing stromal cells surrounded these cells on the mesometrial side. Specific [ 3 H]PGD 2 -binding activity was detected in the decidua of uteri, with PGD 2 synthesis comparable to that of PGE 2 detected in the uteri during the peri-implantation period. Administration of the COX-2-specific inhibitor celecoxib caused adverse effects on decidualization, as demonstrated by the attenuated weight of the implantation sites, which was recovered by the simultaneous administration of a DP agonist. Such a rescuing effect of the DP agonist was mimicked by an EP4 agonist, but not an EP2 agonist. While the importance of DP signaling was shown pharmacologically, DP/EP2 double deficiency did not affect implantation and decidualization, suggesting the contribution of EP4 to these processes. Indeed, administration of an EP4 antagonist substantially affected decidualization in DP/EP2-deficient mice. These results suggest that COX-2-derived PGD 2 and PGE 2 contribute to decidualization via a coordinated pathway of DP and EP4 receptors.
Competing Interests: Conflicts of interest The authors declare that they have no conflicts of interest regarding the contents of this article.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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