Evidence for coordinated interaction of cyclin D3 with p21 and cdk6 in directing the development of uterine stromal cell decidualization and polyploidy during implantation
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Abstract
Uterine decidualization, characterized by stromal cell proliferation, and differentiation
into specialized type of cells (decidual cells) with polyploidy, during implantation
is critical to the pregnancy establishment in mice. The mechanisms by which the cell
cycle events govern these processes are poorly understood. The cell cycle is tightly
regulated at two particular checkpoints, G1-S and G2-M phases. Normal operation of
these phases involves a complex interplay of cyclins, cyclin-dependent kinases (cdks)
and cdk inhibitors (CKIs). We previously observed that upregulation of uterine cyclin
D3 at the implantation site is tightly associated with decidualization in mice. To
better understand the role of cyclin D3 in this process, we examined cell-specific
expression and associated interactions of several cell cycle regulators (cyclins,
cdks and CKIs) specific to different phases of the cell cycle during decidualization
in mice. Among the various cell cycle molecules examined, coordinate expression and
functional association of cyclin D3 with cdk4 suggest a role for proliferation and,
that of cyclin D3 with p21 and cdk6 is consistent with the development of polyploidy
during stromal cell decidualization.