Abstract
Preeclampsia (PE) is a pregnancy-related disease defined as onset of hypertension and proteinuria after the 20th week of pregnancy, which causes most maternal and perinatal morbidity and mortality. Although placental dysfunction is considered as the main cause of PE, the exact pathogenesis of PE is not yet fully understood. Long non-coding RNAs (lncRNAs) are implicated in a broad range of physiological and pathological processes, including the occurrence of PE. In this study, we investigated the expression and functions of HIF-1α pathway–related lncRNA-HEIPP (high expression in PE placenta) in the pathogenesis of PE. The expression of lncRNA-HEIPP in the placenta from women who underwent PE was screened by lncRNA microarray and then verified using real-time polymerase chain reaction. Then, the methylation profile of the lncRNA-HEIPP promoter and the enrichment of H3K4me3 binding were assessed by bisulfite pyrosequencing and chromatin immunoprecipitation (ChIP)–quantitative polymerase chain reaction (qPCR) assay, respectively. It was found that the level of lncRNA-HEIPP in the PE placenta was significantly higher than that in normal placenta and was increased in HTR-8/SVneo human trophoblast cells upon hypoxia treatment. Moreover, we reported that H3K4me3 manifested significantly higher promoter occupancy on lncRNA-HEIPP promoter in HTR-8/SVneo cells upon hypoxia treatment and found that the downregulation of lncRNA-HEIPP promoted trophoblast invasion. Our findings suggested that the hypoxia-induced expression of lncRNA-HEIPP mediated by H3K4me3 modification in trophoblast may contribute to the pathogenesis of PE.
Highlights
Preeclampsia (PE) is a common complication of human pregnancy defined as the occurrence of hypertension and significant proteinuria after the 20th week of gestation, occurring in approximately 3 to 5% of all pregnancies and resulting in about 50,000 maternal deaths annually worldwide (Gormley et al, 2017)
We found that a number of Long non-coding RNAs (lncRNAs) and molecules are closely related with hypoxia inducible factor-1α (HIF-1α) pathway (Figure 2B), and the top 10 lncRNAs (AF064860.7, AC027612.3, RP11-244N9.4, RP11-574M7.1, RP11-80I15.4, RP11-939C17.2, XLOC_013276, AC023085.1, AC009236.1, and RP11-184D12.1) showing mostly dramatic different expression between PE and normal placentas were selected for further validation (Supplementary Table 4)
In the HTR-8/SVneo human trophoblast cell lines, we found that hypoxia could induce the expression of lncRNAHEIPP, which reached the highest level at 24 h upon hypoxia treatment (Figure 3B)
Summary
Preeclampsia (PE) is a common complication of human pregnancy defined as the occurrence of hypertension and significant proteinuria after the 20th week of gestation, occurring in approximately 3 to 5% of all pregnancies and resulting in about 50,000 maternal deaths annually worldwide (Gormley et al, 2017). Recent studies have shown that abnormal trophoblast differentiation, migration, and apoptosis often cause decreased invasion of trophoblast cells and remodeling of uterine spiral artery, resulting in reduced uteroplacental perfusion (Cotechini et al, 2014; Chen and Khalil, 2017; Brosens et al, 2019). This further leads to hypoxia and inflammatory changes in the placenta, which will eventually lead to PE (Harati-Sadegh et al, 2018; Tong and Giussani, 2019). The objective of the current study is to investigate the differentially expressed lncRNAs in human placenta between normal pregnancy and PE and dissect the mechanisms underlying the regulation of lncRNAs by hypoxia as well as their functions in trophoblast cells migration
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
