USP22 regulates the formation and function of placental vasculature during the development of fetal growth restriction.

INTRODUCTION

Fetal growth restriction (FGR) is a common obstetric complication that can lead to a variety of adverse perinatal outcomes and is associated with chronic diseases in adulthood. Since ubiquitin-specific protease 22 (USP22) is closely related to cell growth, differentiation and proliferation, we aimed to investigate the role of USP22 in FGR development.

METHODS

USP22 expression was detected in the placentas of eight normal and eight pregnant women with FGR. To observe changes in the formation and function of placental vasculature, USP22 expression was downregulated in human umbilical vein endothelial cells (HUVECs) using CRISPR/Cas9 and siRNAs. In addition, HUVECs with low and normal USP22 expression were analysed using RNA-seq.

RESULTS

We found that USP22 expression was significantly lower in the placentas of pregnant women with FGR than in normal pregnant women and that HUVECs were unable to survive after USP22 had been knocked out. Moreover, USP22 down-regulation in HUVECs led to decreased proliferation, angiogenesis, vasodilation, apoptosis, and systolic function. RNA-seq identified 3730 differentially expressed genes that were enriched in multiple signalling pathways, including cell cycle regulation, apoptotic signalling, and PI3K/Akt.

DISCUSSION: Together, the findings of this study demonstrate for the first time that abnormal USP22 expression may affect HUVEC proliferation and apoptosis, as well as essential angiogenesis and vasomotor functions during the development of FGR.