Association of β-arrestin1 and p53-Mdm2 signaling in the development of missed abortion

Background Missed abortion is a peculiar form of spontaneous abortion before 20 weeks' gestation. The definite etiology and pathogenesis are not fully understood. Recent studies have demonstrated that p53/Mdm2-mediated ubiquitination of the IGF-1R may be closely related to G-protein-coupled receptor kinases (GRK)/beta-arrestin1 system. Our previous studies have confirmed that the elevated expression of p53 and Mdm2 may be responsible for apoptosis during missed abortion. However, there was no information surrounding beta-arrestin1 in missed abortion. Methods The mRNA levels of beta-arrestin1 in villous samples of 30 missed abortion patients and 31 healthy controls were determined by real-time quantitative polymerase chain reaction (PCR). Immunohistochemistry was used to explore the expression and location of beta-arrestin1, p53, Mdm2, VEGF and HIF-l alpha in trophoblasts. Transwell assays were performed to examine the influences of beta-arrestin1 expression on cell invasion. Furthermore, we tested the effect of beta-arrestin1 on the expression of p53, Mdm2, ERK, AKT and NF-kappa B. Results The expression of beta-arrestin1 in the villous samples of missed abortion group was dramatically lower than control group by quantitative real-time-PCR and immunohistochemistry. Furthermore, the patients with missed abortion showed significantly higher levels of p53, Mdm2, HIF-l alpha and lower level of VEGF than healthy controls by immunohistochemistry. Functional studies showed that suppression of beta-arrestin1 in HTR-8 cells inhibited cell invasion. The protein expressions of ERK and AKT in HTR-8 cells were significantly downregulated by reducing the expression of beta-arrestin1, while the expressions of p53, Mdm2, NF-kappa B were enhanced. Overexpression of beta-arrestin1 exhibited the adverse effect. Conclusion Our data indicated that beta-arrestin1 play an important role in maintaining the maternal-fetal tolerance, the decreased expression of beta-arrestin1 in the villous samples may be related with the development of missed abortion.

Automated summary

The study found that the expression of beta-arrestin1 in villous samples of missed abortion patients was significantly lower than healthy controls, and patients with missed abortion showed altered expression levels of other related proteins. Functional experiments demonstrated that inhibiting beta-arrestin1 can affect cell invasion capability.