Adhesion of trophoblast of the blastocyst to and penetration into the uterine epithelium, invasion into the maternal vessels and endometrial stroma, and establishment of the basic organization of the placenta all occur within the first week following the initiation of implantation in the human, macaques and several other primates. The cellular rearrangements and interactions of trophoblast with endometrial epithelial cells and stroma were studied during this periimplantation stage in macaques. At the early lacunar stage, 1–2 days after the initiation of implantation, both cytotrophoblast and syncytial trophoblast can be found at the maternal surface of lacunae. As the lacunar stage advances, both syncytial trophoblast and cytotrophoblast are found throughout the implantation site including in septae partitioning lacunae, but syncytial trophoblast lines most of the lacunae and forms the confluence with the maternal vessels. Indentations of fetal mesenchyme and accumulation of cytotrophoblast cells within the septae occur rapidly. Over a period of about 2 days, clusters of cytotrophoblast cells pass beyond the syncytial trophoblast at the maternal surface as the anchoring villi, establishing the trophoblastic shell. The bypassing of epithelial plaque cells by cytotrophoblast cells and elimination of stromal matrix between such clusters verifies that this is a progressive invasion rather than simply superficial growth. Concomitant with establishment of the trophoblastic shell there is extravasation of blood, necrosis of plaque cells, and massive invasion of vessels by cytotrophoblast resulting in a necrotic zone between the trophoblastic shell and endometrium. It is concluded that only in the brief period of time of establishment of the trophoblastic shell is the full invasive potential of cytotrophoblast realized and that only at this stage does cytotrophoblast demonstrate the type of invasive and migratory behavior which has been achieved with isolated human cytotrophoblast cells in vitro.

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