The role of p21Cip1/CDKN1A in trophoblastic cells and preeclampsia

Aim:

Preeclampsia (PE) is an unpredictable and unpreventable disease leading to maternal and perinatal mortality and morbidity worldwide. As p21's multiple functionalities are fundamental to placental development, the aim of the present study was to enlighten its key roles in proliferation and differentiation. p21 can also operate as transcription factor and its expression is increased in response to different stress factors to arrest the cell cycle and ensure genomic stability, responsible for mediating the cellular response. Especially the functions of the different trophoblast subpopulations depend on the precise coordination of proliferation, differentiation and invasion. p21's involvement in the pathogenesis of PE was studied in detail.

Material:

To provide new insight and get more profound understanding, p21's expression and localization were systematically analyzed in different trophoblastic cell lines and primary placental tissues with early/late onset PE.

Methods:

The related/deregulated pathways were identified using transcriptome-wide profiling. Protein expression was analyzed via immunohistochemically (IHC) staining and Western blot, RNA expression with realtime-PCR. Fusion assays were performed with p21-depleted BeWo and JEG-3 cells using siRNA and forskolin or 8-br-cAMP.

Results:

p21 is expressed in cytotrophoblasts, the syncytiotrophoblast and extravillous cytotrophoblasts of placental tissue. Its expression decreases with gestational age and is altered in PE. Experiments with siRNA against p21 showed that the downregulation of p21 had a negative impact on the fusion capability of BeWo and JEG-3 cells.

Summary:

The cell cycle key player p21 is involved in the pathogenesis of PE and important for the fusion process of trophoblastic cells.