Embryo implantation triggers dynamic spatiotemporal expression of the basement membrane toolkit during uterine reprogramming

Abstract

Basement membranes (BMs) are specialized extracellular scaffolds that influence behaviors of cells in epithelial, endothelial, muscle, nervous, and fat tissues. Throughout development and in response to injury or disease, BMs are fine-tuned with specific protein compositions, ultrastructure, and localization. These features are modulated through implements of the BM toolkit that is comprised of collagen IV, laminin, perlecan, and nidogen. Two additional proteins, peroxidasin and Goodpasture antigen-binding protein (GPBP), have recently emerged as potential members of the toolkit. In the present study, we sought to determine whether peroxidasin and GPBP undergo dynamic regulation in the assembly of uterine tissue BMs in early pregnancy as a tractable model for dynamic adult BMs. We explored these proteins in the context of collagen IV and laminin that are known to extensively change for decidualization. Electron microscopic analyses revealed: 1) a smooth continuous layer of BM in between the epithelial and stromal layers of the preimplantation endometrium; and 2) interrupted, uneven, and progressively thickened BM within the pericellular space of the postimplantation decidua. Quantification of mRNA levels by qPCR showed changes in expression levels that were complemented by immunofluorescence localization of peroxidasin, GPBP, collagen IV, and laminin. Novel BM-associated and subcellular spatiotemporal localization patterns of the four components suggest both collective pericellular functions and distinct functions in the uterus during reprogramming for embryo implantation.

Keywords: Basement membrane; Collagen IV; Goodpasture antigen-binding protein (GPBP); Laminin; Peroxidasin; Uterus.