Preference of Invasive Cytotrophoblast for Maternal Vessels in Early Implantation in the Macaque

Abstract

The interaction of cytotrophoblast with maternal endometrium, especially endometrial blood vessels, was examined in macaque gestational stages between 2 and 8 days after the onset of implantation. Serial sectioning of these early implantation sites allowed immunostaining of consecutive sections with a number of different antibodies, facilitating cell identification. In the earliest implantation site, immunostaining showed that antibody to cytokeratin stained cytotrophoblast, syncytial trophoblast, epithelial plaque and endometrial gland cells. However, only those cytotrophoblast cells near the maternal-fetal border and within vessels showed surface staining for neural cell adhesion molecules and only syncytial trophoblast showed SP1 reactivity. Even at this early stage cytotrophoblast filled the lumen of superficial arterioles, whereas dilated venules contained only a few cytotrophoblast cells. In later stages endovascular cytotrophoblast not only plugged many spiral arterioles but also migrated into the walls of these arterioles, and progressed into deeper coils. Displacement of endothelial cells and disruption of vessel walls were illustrated with antibody to factor VIII, TGFoc, and desmin. Clusters of cytotrophoblast cells at the fetal-maternal interface tended to bypass clusters of epithelial plaque cells and larger clusters of maternal fibroblasts, but readily entered all vascular spaces. Consequently the vascular system constituted a major pathway of invasion, although the arterioles were the only component substantially invaded beyond the trophoblastic-shell/endometrial border.

The role of invasive trophoblast in implantation and placentation of primates

“…As early as 4 days after implantation, cytotrophoblasts have entered the lumen of the spiral arterioles and by 6 days those directly at the implantation site have been plugged by trophoblast [32] (figure 3b,d). In later stages, the trophoblast migrates into the walls of the vessels as well as penetrating into deeper coils [33]. The presence of endovascular trophoblast is paralleled by loss of the vascular endothelium and disruption of vascular smooth muscle cells [33].…”

“…In later stages, the trophoblast migrates into the walls of the vessels as well as penetrating into deeper coils [33]. The presence of endovascular trophoblast is paralleled by loss of the vascular endothelium and disruption of vascular smooth muscle cells [33]. Despite the extensive changes rendered upon the endothelium and its vasculature, decidualization of endometrial fibroblasts is slow in the macaque, although well developed by two months.…”

Comparative studies of placentation and immunology in non-human primates suggest a scenario for the evolution of deep trophoblast invasion and an explanation for human pregnancy disorders

“…Instead, there is a sharp border at the fetal-maternal interface between a cytotrophoblastic shell and the decidua ( consists of sedentary trophoblast cells embedded in extracellular matrix and remains largely intact throughout pregnancy (Pijnenborg et al 1996, Enders & Blankenship 1997). Secondly, although there is early and rapid invasion of trophoblast by the endovascular route (Enders et al 1996), it does not penetrate as deep. Reports differ as to whether it reaches the myometrium in the rhesus macaque (Ramsey et al 1976, Blankenship et al 1993).…”

The Macaque Placenta—A Mini-Review

“…• Trophoblast invasion of spiral arteries is earlier and initially more agressive in the macaque than in humans (Enders et al 1996). …”

“…• The trophoblastic shell (formed by spreading of cytotrophoblasts from the anchoring villi) in the macaque is continous, relatively thick, and sharply delineated from the underlying endometrium (Enders et al 1996). The human shell is less uniform, and the extravillous trophoblast can be seen streaming off into the endometrium.…”