Localization of Cathepsins D and B at the Maternal-Fetal Interface and the Invasiveness of the Trophoblast during the Postimplantation Period in the Mouse

Abstract

A survey of existing data suggests that trophoblast cells produce factors involved in extracellular matrix degradation. In this study, we correlated the expression of cathepsins D and B in the murine ectoplacental cone with the ultrastructural progress of decidual invasion by trophoblast cells. Both proteases were immunolocalized at implantation sites in lysosome-endosome-like compartments of trophoblast giant cells. Cathepsin D, but not cathepsin B, was also detected ultrastructurally in extracellular compartments surrounded by processes of the invading trophoblast containing extracellular matrix components and endometrial cell debris. The expression of cathepsins D and B by trophoblast cells was confirmed by RT-PCR in ectoplacental cones isolated from implantation chambers at gestation day 7.5. Our data addressed a positive relationship between the expression and presence of cathepsin D at the extracellular compartment of the maternal-fetal interface and the invasiveness of the trophoblast during the postimplantation period, suggesting a participation of invading trophoblast cells in the cathepsin D release. Such findings indicate that mouse trophoblast cells might exhibit a proteolytic ability to partake in the decidual invasion process at the maternal-fetal interface.

IL-10 produced by trophoblast cells inhibits phagosome maturation leading to profound intracellular proliferation of Salmonella enterica Typhimurium

“…In rodent and humans with hemochorial placentation, phagocytic ability is a hall-mark of trophoblast differentiation and imparts invasive capacity for tissue remodeling during implantation [31]. The giant trophoblast cells in particular, demonstrate profound phagocytic activity [19].…”

Integral Proteomic Analysis of Blastocysts Reveals Key Molecular Machinery Governing Embryonic Diapause and Reactivation for Implantation in Mice1

“…It is conceivable that active phagocytosis in mural trophoblast cells would damage the membrane integrity of uterine epithelium cells, therefore facilitating epithelial apoptosis. Besides, it has been shown that cathepsins, such as CTSD, could be secreted as proteases into extracellular matrix for postimplantation trophoblast cell invasion and vascular remodeling [65,66]. In women, cathepsins were extensively expressed in first trimester placenta, the invasive phase of placentation, indicating the involvement of these proteases in trophoblast invasion [67,68].…”

Elevated serum cathepsin B concentration in pregnant women is associated with preeclampsia

“…The cathepsin proteases are major lysosomal enzymes that are important for placental development, in mice [5] as well as humans [6,7]. In general, these enzymes are involved in protein degradation and processing, and have been implicated in a variety of cellular processes, such as apoptosis, angiogenesis, cell proliferation, and invasion [6].…”

“…It is reportedly correlated with invasion and phagocytic activity in rodent trophoblasts [10]. Several studies on animal studies have indicated the roles of CB and CD in normal and pathologic placentation [5,10,11]. However, research on changes in serum concentrations of cathepsins in PE in humans is limited, although one study reported significantly elevated serum levels of CB and CL in PE [12].…”