Par3/integrin β1 regulates embryo adhesion via changing endometrial luminal epithelium polarity†

Abstract

The objective is to investigate the pathophysiological significance of Par3 and integrin β1 with regard to the functionality of the endometrial luminal epithelium (LE). Design: laboratory study; setting: university research laboratory. Analysis involved endometrial aspirates and endometrial adenocarcinoma cells (HEC-1A) and endometrial carcinoma cells (RL95-2). We first examined the expression and localization of Par3 and integrin β1 in HEC-1A cells and RL95-2 cells. Then we knocked down Par3 and integrin β1 in HEC-1A cells and RL95-2 cells, respectively, and found that Par3/integrin β1 affected embryo adhesion by regulating the intercellular tight junctions' (TJs') structure and thus the polarity of the endometrial LE. These findings were also confirmed in the endometrium specimens from human and mice. The main outcome measures were the expression and localization of Par3 and integrin β1 in the endometrial epithelial cell lines and endometrium specimens and the regulations of Par3 and integrin β1 on TJs, polarity, and embryo adhesion. Following the knockdown of Par3 in HEC-1A cells, there was a reduction in the complexity of the TJs and cell polarity, and the adhered blastocysts number was significantly increased. However, the reduction of integrin β1 in RL95-2 cells resulted in effects that directly opposed those following the knockdown of Par3 in HEC-1A cells. Estrogen and progesterone reduced the expression of Par3 and promoted the expression of integrin β1 in HEC-1A cells. Par3/integrin β1 regulates embryo adhesion by regulating intercellular TJs' structure and polarity of endometrial LE under the action of ovarian hormones.

Keywords: Par3; embryo adhesion; integrin β1; luminal epithelial cell polarity; tight junction.