Modification of uterine vasculature during pregnancy in macaques.

Abstract

Embryonic development in macaques includes extensive modification of the uterine vasculature by fetal trophoblast cells. Soon after the onset of blastocyst attachment to the endometrium, syncytial trophoblast cells intrude between endometrial epithelial cells, resulting in focal epithelium loss. Trophoblast cells continue to move into the endometrial stroma and encounter superficial uterine capillaries. These capillaries are penetrated by trophoblast, which permits maternal blood to leave the maternal circulation and enter lacunae formed within the mass of trophoblast cells. Cytotrophoblast cells enter the uterine vessels and attach to the endothelium via cell adhesion molecules prior to migration into confluent spiral arterioles, against the flow of blood. As intra-arterial cytotrophoblast cells migrate, they displace adjacent endothelium, produce matrix metalloproteinases, traverse the tunica intima, and reside in the tunica media as intramural trophoblast. Intramural trophoblast cells disrupt the tunica media and become surrounded by an extensive extracellular matrix. In areas proximal to the placenta, the entire circumferences of spiral arteries are modified in this way. In the same arteries, distal to the placenta and farther "upstream," trophoblast-mediated changes to the arterial wall are less extensive. Uterine veins are modified by trophoblast only in the area immediately next to the trophoblast shell, with no trophoblast migration. The functional consequence of this trophoblast activity may be to ensure an adequate flow of maternal blood to the placenta, thus enhancing the survival of the fetus.