Identification of 72-kilodalton type IV collagenase at sites of trophoblastic invasion of macaque spiral arteries.

The walls of uterine spiral arteries are invaded by extravillous trophoblast cells and are thereby converted to the uteroplacental arteries of pregnancy. The mechanisms by which this invasion occurs are not understood, but the extracellular matrices that are breached suggest participation by specific proteinases. In this report we describe the immunohistochemical localization of 72-kd type IV collagenase (gelatinase A or MMP-2) among intra-arterial trophoblast cells and endometrial cells during development of macaque uteroplacental arteries. Cytokeratin-positive trophoblast cells were identified within arteries at each stage studied (between days 22-128 of gestation). Many of these cells, whether located in the arterial lumen or within the vessel wall, were immunoreactive for the proteinase. Early in the invasive process these trophoblast cells were associated with discontinuities of the endothelial basement membrane and later became interspersed with smooth muscle cells of the tunica media. While trophoblast cells comprised the entire thickness of the arterial wall in many locations, typically only a subset of these cells expressed the proteinase. Many endometrial stromal cells were also immunoreactive for the proteinase, as were some arterial endothelial and smooth muscle cells. It is concluded that this, and probably other, proteinases are active throughout gestation in the restructuring of uterine spiral arteries and other endometrial tissues as necessary to accommodate the development of the fetus.