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Increased apoptosis in first trimester extravillous trophoblasts from pregnancies at higher risk of developing preeclampsia.

ABSTRACT: Preeclampsia complicates 5 to 10% of pregnancies and is a leading cause of maternal and fetal mortality and morbidity. Although the cause is unknown, inadequate invasion and remodeling of maternal uterine arteries by extravillous trophoblasts (EVTs) in the first trimester is a common feature. Uterine spiral artery resistance as detected by Doppler ultrasound is commonly used in the second trimester to identify pregnancies destined to develop preeclampsia. Correlation between high uterine resistance and the failure of trophoblast invasion has been reported as early as 12 weeks. However, the reason for this failure has not been established. Understanding the processes involved would significantly improve our diagnostic potential. In this study, we correlated increased first trimester uterine artery resistance with a biological abnormality in trophoblast function. EVTs derived from high-resistance pregnancies were more sensitive to apoptotic stimuli than those from normal-resistance pregnancies. Survival of EVTs from high-resistance pregnancies could be increased by nitric oxide, whereas inhibition of nitric oxide in cells from normal-resistance pregnancies increased apoptotic sensitivity. This predates the onset of symptoms by several weeks and provides evidence for a mechanism responsible for the incomplete uterine vessel remodeling and the differences in artery resistance between preeclamptic and normal pregnancies.

SUBMITTER: Whitley GS

PROVIDER: S-EPMC1899436 | biostudies-literature | 2007 Jun

REPOSITORIES: biostudies-literature

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Increased apoptosis in first trimester extravillous trophoblasts from pregnancies at higher risk of developing preeclampsia.

Whitley Guy St J GS Dash Philip R PR Ayling Laura-Jo LJ Prefumo Federico F Thilaganathan Baskaran B Cartwright Judith E JE

The American journal of pathology 20070601 6

Preeclampsia complicates 5 to 10% of pregnancies and is a leading cause of maternal and fetal mortality and morbidity. Although the cause is unknown, inadequate invasion and remodeling of maternal uterine arteries by extravillous trophoblasts (EVTs) in the first trimester is a common feature. Uterine spiral artery resistance as detected by Doppler ultrasound is commonly used in the second trimester to identify pregnancies destined to develop preeclampsia. Correlation between high uterine resista ...[more]

PMID: 17525258

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Project description:Purpose: During early placentation, extravillous trophoblast (EVT) cell invasion into maternal decidua plays a crucial role in establishment of the successful pregnancy. However, little is known about the characteristic features of EVT-associated ncRNAs. The purpose of this study is to elucidate gene expression profile for both coding and non-coding genes (i.e., mRNAs, lncRNAs, and miRNAs) expressed in EVT cells isolated from the first-trimester human placenta by RNA sequencing analysis. Methods: Human first trimester placental tissues (at gestational week 7, n=3) were obtained after legal abortions. EVT cells growing from explanted human chorionic villi were isolated. Minced chorionic villous tips were defined as first-trimester chorionic villous trophoblast (CVT) cells. Using total RNAs of these samples, mRNA/lncRNA-sequencing analysis was carried out on an Illumina MiSeq (San Diego, California, USA) using MiSeq v2 Reagent Kit 300cycle (cat. no. MS-102-2002; Illumina) and MiSeq v2 Reagent Kit 50cycle (cat. no. MS-102-2001; Illumina), respectively. The paired-end reads of 151 bp length for mRNA/lncRNA-sequencing and single reads of 26 bp length for miRNA-sequencing were obtained as fastq files which were imported into CLC genomics workbench (version 8.0.1; Qiagen, Venlo, Netherlands). Clean reads were aligned to the human genome sequence retrieved from the Ensembl database (Assembly GRCh38.p13, database version 82.38 and 101.38) and microRNA database miRbase (release 21), using CLC Genomics Workbench Map Reads to Reference tool. Normalization of gene expression data was performed by the TMM method of edgeR package. Statistically differentially expressed transcripts were conducted using edgeR. Genes that had a false discovery rate (FDR)-corrected p-value (q-value) of < 0.05 and an absolute log2 fold change (log FC) ≥ 1 were judged to be significantly differentially expressed (i.e., differentially expressed genes, DEGs). Results: Five thousand ninty-two mRNAs , 422 lncRNAs and 400 miRNAs were found to be differentially expressed. One hundred differentially expressed genes (i.e., 10 mRNAs, 7 lncRNAs, and 83 miRNAs) that are located in the chromosome 14q32.2 region containing the eutherian-specific imprinted DLK1-DIO3 domain were significantly down-regulated in EVT cells. In terms of imprinted genes (http://www.geneimprint.com/site/genes-by-species), 68 genes were found to be differentially expressed; 71% of these genes were down-regulated in EVT cells. lncRNA H19 was a DEG (q = 1.29.E-09, log FC = 2.98) and the most highly expressed lncRNA (70.47%) in EVT cells. Conclusions: The present research should be valuable for a resource for future ncRNA research in EVT cells.

Dataset Information

Increased apoptosis in first trimester extravillous trophoblasts from pregnancies at higher risk of developing preeclampsia.

Publications

Increased apoptosis in first trimester extravillous trophoblasts from pregnancies at higher risk of developing preeclampsia.

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