Pregnancy

Temporal and Spatial Expression of Integrins and Their Extracellular Matrix Ligands at the Maternal-Fetal Interface in the Rhesus Monkey During Pregnancy

Abstract

The integrin and extracellular matrix protein (ECM) mediated adhesion and invasion of the receptive maternal uterine endometrium by trophoblasts is a critical event in the complex physiological process of pregnancy. Although the process has been largely revealed in mice, the relevant mechanism in primates remains unclear. In this paper, we describe the expression patterns and dynamic alterations of integrin subunits (1, 5, 6, 1 and 4) as well as their ECM ligands, such as laminin (LN), type IV collagen (Col IV) and fibronectin (FN) at the maternal-fetal interface during gestational day 15, 25, 50, 100 and full term in 20 pregnant rhesus monkeys. Immunohistochemistry and in situ hybridization revealed that a relatively high expression of integrins occurred in trophoblast cells at gestational day 15 with the peak level occurring at day 25. The expression level decreased from day 50 to term. Along the invasive pathway, expression levels of integrin a1, a5, and b1 subunits were gradually elevated from the proximal to distal column reaching peak level in the trophoblast shell, but reduced in those invasive EVCT cells in contact with the decidua. Integrin 1, 5, 1 and 4 subunits were also highly expressed in decidual stromal cells and moderately expressed in the maternal epithelium and endothelium. Immunoreactive FN, LN and Col IV were distributed in extravillous cytotrophoblast (EVCT), decidual stromal cells and part of the uterine epithelial and endothelial cells. These data suggest that the correlated expression of integrins and their ECM ligands at the maternal-fetal interface might be involved in regulation of cell proliferation and differentiation as well as the counterbalanced invasion-accelerating and invasion-restraining processes in trophoblast cells during the early stage of pregnancy.