Uterine WNTS modulates fibronectin binding activity required for blastocyst attachment through the WNT/CA2+ signaling pathway in mice

Reproductive Biology and Endocrinology

Research

Laurie Pinel¹  Daniel Dufort¹  Yuefei Lou² 

[1] Department of Obstetrics and Gynecology, McGill University, H4A 3J1, Montreal, QC, Canada;Child Health and Human Development Program, H4A 3J1, Montreal, QC, Canada;Research Institute of the McGill University Health Centre, H4A 3J1, Montreal, QC, Canada;Department of Obstetrics and Gynecology, McGill University, H4A 3J1, Montreal, QC, Canada;Department of Critical Care Medicine, Cumming School of Medicine, University of Calgary, T2N 1N4, Calgary, AB, Canada;

关键词: Wnt signaling;    Embryo implantation;    Integrins;    Fibronectin binding;    Mouse blastocyst;    Trophectoderm;    Wnt/Ca;    Non-canonical wnt signaling;   

DOI  :  10.1186/s12958-023-01135-0

 received in 2023-06-21, accepted in 2023-09-08,  发布年份 2023

来源: Springer

【 摘 要 】

Adhesion of the implanting blastocyst involves the interaction between integrin proteins expressed by trophoblast cells and components present in the basement membrane of the endometrial luminal epithelium. Although several factors regulating integrins and their adhesion to fibronectin are already known, we showed that Wnt signaling is involved in the regulation of blastocyst adhesion through the trafficking of integrins expressed by trophoblast cells. Localization of Itgα5β1 by immunofluorescence and FN-binding assays were conducted on peri-implantation blastocysts treated with either Wnt5a or Wnt7a proteins. Both Wnt5a and Wnt7a induced a translocation of Itgα5β1 at the surface of the blastocyst and an increase in FN-binding activity. We further demonstrated that uterine fluid is capable of inducing integrin translocation and this activity can be specifically inhibited by the Wnt inhibitor sFRP2. To identify the Wnt signaling pathway involved in this activity, blastocysts were incubated with inhibitors of either p38MAPK, PI3K pathway or CamKII prior to the addition of Wnts. Whereas inhibition of p38MAPK and PI3K had not effect, inhibition of CamKII reduced FN-binding activity induced by Wnts. Finally, we demonstrated that inhibition of Wnts by sFRP2 reduced the binding efficiency of the blastocyst to uterine epithelial cells. Our findings provide new insight into the mechanism that regulates integrin trafficking and FN-binding activity and identifies Wnts as a key player in blastocyst attachment to the uterine epithelium.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

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