Abstract
To determine the function of Annexin A2 (Axna2) in mouse embryo implantation in vivo, experimental manipulation of Axna2 activities was performed in mouse endometrial tissue in vivo and in vitro. Histological examination of endometrial tissues was performed throughout the reproduction cycle and after steroid treatment. Embryo implantation was determined after blockage of the Axna2 activities by siRNA or anti-Axna2 antibody. The expression of Axna2 immunoreactivies in the endometrial luminal epithelium changed cyclically in the estrus cycle and was upregulated by estrogen. After nidatory estrogen surge, there was a concentration of Axna2 immunoreactivities at the interface between the implanting embryo and the luminal epithelium. The phenomenon was likely to be induced by the implanting embryos as no such concentration of signal was observed in the inter-implantation sites and in pseudopregnancy. Knockdown of Axna2 by siRNA reduced attachment of mouse blastocysts onto endometrial tissues in vitro. Consistently, the number of implantation sites was significantly reduced after infusion of anti-Axna2 antibody into the uterine cavity. Steroids and embryos modulate the expression of Axna2 in the endometrial epithelium. Axna2 may function as an adhesion molecule during embryo implantation in mice.
Highlights
Embryo implantation consists of 3 tightly regulated events, namely apposition, adhesion and penetration
The results show that estradiol (E2) controls annexin A2 (Axna2) expression in the luminal epithelium (LE) of mice, and that the implanting embryos modulate the expression of Axna2 at the implantation sites
While there are some in vitro data using cell lines to represent embryo and LE during implantation supporting a role of Axna2 in human implantation, the regulation of Axna2 during doi:10.1371/journal.pone.0139506.g004
Summary
Embryo implantation consists of 3 tightly regulated events, namely apposition, adhesion and penetration. Annexin A2 Acts on Implantation in Mice. We determined the differentially regulated surface proteins on receptive (4 pm of Day 4 of pregnancy) endometrial luminal epithelium (LE) relative to nonreceptive (Day 1 of pregnancy) LE in mice using biotin labeling followed by 2-dimensional gel electrophoresis and tandem mass spectrometry. Our unpublished results showed a 2-fold increase in the expression of annexin A2 (Axna2) in the mouse receptive LE, a result similar to that in human endometrium [4,5,6]. AXAN2 was recently identified as one of the apical surface molecules in a receptive human endometrial cell line [7]
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