The role of p53‐MDM2 signaling in missed abortion and possible pathogenesis

Abstract

Background: Missed abortion is one of the common obstetrical and gynecological complications, angiogenesis is the most important factor in fetal and placental development. However, the definite etiology and pathogenesis are not fully understood. Methods: The mRNA levels of p53, MDM2, VEGF, and HIF-lα were detected in 60 villous samples of missed abortion patients and 64 healthy controls by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Immunohistochemistry was used to explore the expression and correlation of p53, MDM2, VEGF, and HIF-lα in villous tissues. Furthermore, we upregulated MDM2 expression in JEG-3 and BeWo cells under hypoxia, combined with Nutlin3, the cell cycle was determined using flow cytometry and the expressions of p53, MDM2, VEGF, and HIF-1α were determined by qRT-PCR and western blot.Results: qRT-PCR demonstrated that the expressions of p53, MDM2, and HIF-1α were significantly increased and VEGF was decreased in missed abortion group compared with normal pregnancies. Correlation analysis found that p53 was positively correlated with MDM2 and HIF-1α, and negatively correlated with VEGF in missed abortion group. After administration of Nutlin3, overexpression of MDM2 could arrest cell cycle in G1 phase and reduce the proportion of S phase. The expression of p53 and MDM2 of JEG-3 cells and BeWo cells which transfected with pcDNA3.1-MDM2 plasmid were markedly increased after Nutlin3 addition under hypoxic conditions, while the expression of VEGF and HIF-1α decreased. Conclusion: Our data indicated that during the development of villi in early pregnancy, p53-MDM2 signaling regulate cell cycle and angiogenesis through interaction with HIF-1α and VEGF, which may be a crucial factor affecting pregnancy outcomes.

Association between HIF‐1α, BNIP3, and autophagy in the chorionic villi of missed abortion

“…Tentative evidence indicates that autophagy occurs during the fertilization process for the oocyte‐to‐embryo transition, but how autophagy affects embryonic development remains unclear 30 . Defective embryonic development is one of the most common causes of missed abortion 31 . The present study had clear limitations, primarily because of the lack of karyotype analysis of chorionic villi.…”

“…30 Defective embryonic development is one of the most common causes of missed abortion. 31 The present study had clear limitations, primarily because of the lack of karyotype analysis of chorionic villi. The changes in HIF-1α expression and autophagy state in the villi of missed abortion would be due to either fetal or placental abnormalities, and these levels in other parts of the placenta and in the embryo remain unknown.…”

HTR1B regulates mitochondrial homeostasis and mitophagy by activating the ERK/ MAPK signalling pathway during human embryonic arrest

“…The incidence of EA is escalating annually, posing a pressing clinical challenge. Consequently, the etiology and pathogenesis of EA have become a prominent research area in reproductive science [ 26 ]. Our research endeavours have provided valuable insights into the prevention and treatment of this condition.…”