Differential expression of G1 cyclins during human placentogenesis.

Cyclins are proteins that support the progression of cell-cycle stages in proliferating cells. The purpose of this study was to determine which of the cyclin genes is involved in the regulation of normal human trophoblast proliferation. The presence and cellular localization of four G1 cyclins D1, D2, D3 and E, were determined by immunohistochemistry. This analysis indicated that cyclins E and D3 are the predominant cyclins in villous trophoblast. D2 was present only within the villous core, in fetal macrophages. Positive immunoreactivity for cyclin D1 was strongest in second and third trimester placentae, in the cells lining the intravillous vessels with additional reactivity in extravillous cytotrophoblasts. Because cyclin E protein was present in a greater percentage of cells than those that are dividing, Western blot analysis was performed to validate the fidelity of the immunohistochemistry data. The results of the Western analysis revealed that two forms of cyclin E protein of the appropriate size were present. Data collected from this study suggest that within the trophoblast lineage, cyclins D3 and E are important cell cycle regulatory proteins, and further, that cyclin E may function in trophoblast terminal differentiation as well.