A repertoire of cell cycle regulators whose expression is coordinated withhuman cytotrophoblast differentiation

Although placental development depends on careful coordination of trophobla st proliferation and differentiation, little is known about the mitotic reg ulators that are key to synchronizing these events. We immunolocalized a br oad range of these regulators in tissue sections of the maternal-fetal inte rface (first trimester through term) that contained floating villi (which i nclude cytotrophoblasts differentiating into syncytiotrophoblasts) and anch oring villi (which include cytotrophoblasts differentiating into invasive c ells). Trophoblast populations at the maternal-fetal interface stained for 16 of the cell cycle regulators whose expression we studied The staining pa tterns changed as a function of both differentiation and gestational age. D ifferentiation along the invasive pathway was associated with entrance into , then permanent withdrawal from, the cell cycle, as evidenced by the orche strated expression of cyclins, their catalytic subunits, and inhibitors. Su rprisingly, we found coexpression of molecules that regulate different port ions of the cell cycle in the syncytium, These data, which constitute one o f the few examples to date of is situ localization of an extensive repertoi re of mitotic regulators, provide the basis for studies aimed at understand ing factors that lead to abnormal placentation.