Functional analysis of RITA in trophoblastic cell fusion and preeclampsia

Aim:

Preeclampsia (PE) is one of the leading causes of maternal and perinatal mortality and morbidity worldwide. PE, a pregnancy-specific disorder, originates from the placenta. Despite intensive research, its pathogenesis is not well understood and no therapy is currently available. It is of clinical relevance to decipher new molecular targets and biomarker. RITA, the RBP-J interacting and tubulin-associated protein, has been identified as a negative modulator of the Notch pathway and as a microtubule binding protein.

Material:

RITA's expression and localization was systematically studied in different trophoblastic cell lines and primary placental tissues from patients with early and late onset PE.

Methods:

Protein expression was analyzed via immunohistochemically (IHC) staining and Western blot, RNA expression with realtime-PCR. Fusion assays were performed with RITA-depleted BeWo and JEG-3 cells using siRNA and forskolin.

Results:

RITA is expressed in different trophoblastic cell lines and in primary placental tissue, especially in the proliferative villous cytotrophoblasts and the terminally differentiated, non-proliferative, multinucleated and highly metabolic syncytiotrophoblast. The expression of RITA is decreased in early onset PE of patients with a normal body mass index and its deficiency is associated with reduced β-hCG measurements in trophoblastic cells.

Summary:

RITA is expressed in the placenta and decreases with gestational age. Its RNA level is decreased in early onset PE primary samples and its deficiency is associated with the reduced fusion capacity of BeWo cells. RITA seems to play an important role in placental development and PE.