In:
American Journal of Reproductive Immunology, Wiley, Vol. 81, No. 5 ( 2019-05)
Abstract:
To test whether lipoxin A4 (LXA4) interferes with embryo implantation via suppression of epithelial‐mesenchymal transition (EMT). Method of study We developed a mouse model of LXA4 blocking embryo implantation and detected the indicators of EMT to confirm that LXA4 inhibits EMT might be a mechanism of interfering with the embryo implantation. We detected integrin‐linked kinase (ILK), N‐formylpeptide receptor 2 (FPR2), vascular endothelial growth factor, matrix metalloproteinases (MMPs), Akt, GSK3β, NF‐ĸB, twist, vimentin, fibronectin, and β‐catenin mRNA expression using reverse transcriptase‐polymerase chain reaction (RT‐PCR) and real‐time RT‐PCR; localized protein expression using immunohistochemistry and Western blotting assay; MMPs activity assay by gelatin zymography; and the status of implantation in pregnant animals assessed by pontamine blue reaction test. Results Preimplantation administration of LXA4 resulted in implantation failure. LXA4 has a time‐ and dose‐dependent effect on embryo implantation. Day 0.5 after fertilization is the most effective time to use LXA4 to block embryo implantation. (a) LXA4 reduced endometrial stroma edema; (b) LXA4 inhibited the activity of MMP9 and significantly upregulated the expression of β‐catenin, and downregulated the expression of vimentin, fibronectin, twist, NF‐κB, Akt, and Gsk‐3β in the endometrium and TEV‐1 cells; (c) LXA4 upregulated the expression of FPR2, and downregulated the expression of ILK; FPR2‐overexpressing had an inhibitory effect on ILK in TEV‐1 cells. Conclusion LXA4 inhibits EMT which attenuates ILK action by enhancing FPR2; therefore, this might be a mechanism of interfering with embryo implantation.
Type of Medium:
Online Resource
ISSN:
1046-7408
,
1600-0897
DOI:
10.1111/aji.2019.81.issue-5
Language:
English
Publisher:
Wiley
Publication Date:
2019
detail.hit.zdb_id:
2024667-5
