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Lipoxin A4 (LXA4), a biologically active eicosanoid with specific anti-inflammatory and pro-resolving properties, was recently found to be a novel modulator of estrogen receptor \u03b1 (ER\u03b1). In this study, we investigated the potential role of LXA4 in implantation. We found that LXA4 blocked embryo implantation in mice and significantly reduced the expression of inflammatory mediators associated with uterine receptivity and embryo implantation, including corticotropin-releasing factor (CRF), cyclooxygenase 2-derived prostaglandin I2 and prostaglandin E2, leukemia inhibitory factor, and interleukin 6, but this effect was independent of LXA4 receptor. Subsequent investigation revealed enhanced ER\u03b1 activity in the uteri of LXA4-treated mice during the peri-implantation period. ER\u03b1 and phosphorylated ER\u03b1 were significantly increased following LXA4 treatment. Finally, it was demonstrated that the inhibitory effect of LXA4 on embryo implantation was mediated through ER\u03b1. In the presence of the ER\u03b1 antagonist ICI 182 780, LXA4 failed to block embryo implantation. LXA4 also failed to inhibit CRF expression. These results suggested that LXA4 blocks embryo implantation by controlling ER\u03b1 activity, and this effect appeared to be related to the suppression of the inflammatory microenvironment necessary for implantation.<\/jats:p>","DOI":"10.1530\/rep-12-0469","type":"journal-article","created":{"date-parts":[[2013,2,21]],"date-time":"2013-02-21T01:54:31Z","timestamp":1361411671000},"page":"411-420","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":16,"title":["Lipoxin A4 blocks embryo implantation by controlling estrogen receptor \u03b1 activity"],"prefix":"10.1093","volume":"145","author":[{"given":"Jing","family":"Xiong","sequence":"first","affiliation":[{"name":"Institute of Pathology , Tongji Hospital 2 , Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China"},{"name":"Department of Pathophysiology , Tongji Hospital 2 , Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pan","family":"Zeng","sequence":"additional","affiliation":[{"name":"Institute of Pathology , Tongji Hospital 2 , Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China"},{"name":"Department of Pathophysiology , Tongji Hospital 2 , Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xue","family":"Cheng","sequence":"additional","affiliation":[{"name":"Institute of Pathology , Tongji Hospital 2 , Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China"},{"name":"Department of Pathophysiology , Tongji Hospital 2 , Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of 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