The Up-Regulation of TP53 Impairs Decidualization by Promoting Apoptosis of Decidual Stromal Cells in Unexplained Recurrent Spontaneous Abortion

Abstract

Abstract Objectives: This study aims to clarify the regulation mechanism of TP53 in the impaired decidualization of unexplained recurrent spontaneous abortion (URSA).Methods: RNA-seq analysis was conducted on decidual stromal cells (DSCs) from patients with URSA and healthy controls. TP53 overexpression lentivirus and TP53 shRNA lentivirus were respectively transfected into the human endometrial stromal cell (ESC) line before induced decidualization in vitro. And then apoptosis and decidualization markers were examed. In addition, the long non-coding RNA (lncRNA) UNQ6494 overexpressed plasmid was constructed and transfected into primary ESCs with lentivirus before induced decidualization according to the results of RNA-seq and bioinformatics analysis, and cell cycle-related indicators were detected by RT-PCR.Results: 2557 differentially expressed transcripts (DETs) in URSA were identified by RNA-seq, which were mainly enriched in the p53 signaling pathway. Besides, lncRNA UNQ6494 was closely related to p53 in the transcriptome analysis. After infected with TP53, the apoptosis of DSCs was increased through p53/bax signal transduction in the process of decidualization in vitro and the level of decidualization markers PRL and IGFBP1 were decreased. Besides, over expressed lncRNA UNQ6494 increased the mRNA level of ATM, ATR, p53 as well as affected the level of p21, cycline and CDK2 that were associated with cell cycle arrest, which may be the intrinsic cause accounting for the activation of p53/bax dependent apoptosis.Conclusion: The activation of p53/bax dependent apoptosis in ESCs impaires decidualization in URSA, which may be closely related to lncRNA UNQ6494 and cell cycle arrest.