Annexin A2 Acts as an Adhesion Molecule on the Endometrial Epithelium during Implantation in Mice

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.

Determination of Highly Sensitive Biological Cell Model Systems to Screen BPA-Related Health Hazards Using Pathway Studio

“…The study demonstrated that disruption of the maternal MTHFD1 gene damages fetal growth [ 86 ]. There are also ample studies that suggest ANXA2 is closely involved with embryo implantation and breast cancer, by acting as an adhesion molecule on the endometrium [ 87 , 88 , 89 ].…”

Identification of 56 Proteins Involved in Embryo–Maternal Interactions in the Bovine Oviduct

“…Annexin A1 knock-out female mice displayed numerous changes in early gestation, including increased sites of implantation, increased inflammatory reaction in the uterine fluid during implantation, reduced pre-and post-implantation losses and enhanced plasma progesterone [46]. Furthermore, ANXA2 was shown to be crucial for embryo adhesiveness to the endometrium, a critical step for implantation, in humans [47] and mice [48].…”

Adhesion molecules in gamete transport, fertilization, early embryonic development, and implantation—role in establishing a pregnancy in cattle: A review

“…For example, annexin A1 and annexin A2 were reported to have a lesser expression in the chorioamnion and adjacent uterine caruncles for embryos with retarded development compared to embryos with normal development in the Italian Mediterranean River buffalo (Balestrieri et al, 2013; Strazzullo et al, 2014). Annexin A2 has been specifically implicated in embryo attachment in humans (Barone & Heisenberg, 2012; Garrido‐Gomez et al, 2012) and mice (Wang et al, 2015), while annexin A1 is involved with general cell adhesion (Horlacher et al, 2011). The studies in River Buffalo provided a clear demonstration of altered adhesion molecule function in a well‐characterized model of retarded embryonic development (Campanile, Neglia, & D'Occhio, 2016).…”