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Plasma samples from pregnant who developed preeclampsia and remained healthy along pregnancy (controls)

ABSTRACT: Preeclampsia (PE) is a major health problem in pregnancy, and miRNAs play a role in the pathophysiology of PE. However, the expression of circulating miRNAs was not analyzed in the second trimester of pregnancy, a period of major relevance to identify predictive biomarkers for PE. Therefore, we examined the expression profiles of 84 circulating miRNAs using PCR-array in plasma collected between 20 and 25 weeks of gestation from pregnant who subsequently developed PE and from those who remained healthy along pregnancy randomly selected from a prospective cohort of pregnant. miR-204-5p (P=0.0082) and other 22 miRNAs were upregulated (fold change > 2.0, while miR-24-3p, miR-22-3p, miR-143-3p, and miR-376c-3p had fold change > 4.0) and six miRNAs were downregulated (fold change < 0.5) in plasma from pregnant who developed PE. Target genes for differentially expressed miRNAs were extracted from the miRTarBase of experimentally validated miRNA-target interactions and used in gene set functional enrichment and REACTOME pathway analysis. The 20 pathways with the lowest false discovery rate for the upregulated and downregulated miRNAs are related to pathophysiology of PE, such as apoptosis, angiogenesis, and signal transduction, including signaling by receptor tyrosine kinases, VEGF and TGFB family members. Moreover, we explored the 37 target genes and pathways for miR-204-5p, including MMP-9, MALAT1, TGFBR2, and SIRT1. The circulating miRNAs differentially expressed in the second trimester of pregnancy are related to target genes and pathways of pathophysiological relevance during the early development of PE, and our findings provide for potential circulating predictive biomarkers in PE. For the PCR array, total RNA isolated was converted into cDNA using the miScript II RT Kit (Qiagen®, Leusden, Netherlands), according to the manufacturer’s instructions

ORGANISM(S): Homo sapiens

PROVIDER: GSE168860 | GEO | 2021/03/15

REPOSITORIES: GEO

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Project description:Low fertility remains a leading cause of poor productivity in dairy cattle. In this context, there is significant interest in developing novel tools for accurate early diagnosis of pregnancy. MicroRNAs (miRNAs) are short RNA molecules which are critically involved in regulating gene expression during both health and disease. MiRNAs have been shown to regulate ovarian function, uterine receptivity, embryonic development and placental function. Circulating miRNAs can provide useful biomarkers of tissue function and disease; importantly, differential miRNA profiles have been linked to pregnancy and preeclampsia in humans. This study sought to establish the potential of circulating miRNAs as biomarkers of early pregnancy in cattle. We applied Illumina small-RNA sequencing to profile miRNAs in plasma samples collected from eight non-pregnant heifers on Days 0, 8 and 16 of the oestrous cycle and 11 heifers on Days 16 and 24 of pregnancy. We sequenced a total of 46 samples and generated 9.2 million miRNA reads per sample. There were no differences in miRNA read abundance between any of the pregnant and non-pregnant time-points (FDRâ>â0.1). As a complementary approach, we analysed sample pools (3-4 samples/pool) corresponding to Days 0, 8 and 16 of the oestrous cycle and Day 24 of pregnancy (nâ=â3 pools/group) using Qiagen PCR arrays. A total of 16 miRNAs were differentially expressed (FDRâ<â0.1) in plasma between pregnant and non-pregnant animals. RT-qPCR validation using the same plasma samples confirmed that miR-26a was differentially upregulated on Day 16 pregnant relative to non-pregnant heifers (1.7-fold; Pâ=â0.043), whereas miR-1249 tended to be upregulated in Day 16 pregnant heifers (1.6-fold; Pâ=â0.081). Further validation in an independent group of heifers confirmed an increase in plasma miR-26a levels during early pregnancy, which was significant only on Day 24 (2.0-fold; Pâ=â0.027). Through genome-wide analyses we have successfully profiled plasma miRNA populations associated with early pregnancy in cattle. We have identified miR-26a as a potential circulating biomarker of early pregnancy. Sequencing of three sequencial samples from each of eight cycling animals (Days 0, 8 and 16, total 24 samples) and two samples from each of 11 pregnant animals (Days 16 and 24, total 22 samples). Main comparisons were between non-pregnant and pregnant groups

Project description:Low fertility remains a leading cause of poor productivity in dairy cattle. In this context, there is significant interest in developing novel tools for accurate early diagnosis of pregnancy. MicroRNAs (miRNAs) are short RNA molecules which are critically involved in regulating gene expression during both health and disease. MiRNAs have been shown to regulate ovarian function, uterine receptivity, embryonic development and placental function. Circulating miRNAs can provide useful biomarkers of tissue function and disease; importantly, differential miRNA profiles have been linked to pregnancy and preeclampsia in humans. This study sought to establish the potential of circulating miRNAs as biomarkers of early pregnancy in cattle. We applied Illumina small-RNA sequencing to profile miRNAs in plasma samples collected from eight non-pregnant heifers on Days 0, 8 and 16 of the oestrous cycle and 11 heifers on Days 16 and 24 of pregnancy. We sequenced a total of 46 samples and generated 9.2 million miRNA reads per sample. There were no differences in miRNA read abundance between any of the pregnant and non-pregnant time-points (FDR > 0.1). As a complementary approach, we analysed sample pools (3-4 samples/pool) corresponding to Days 0, 8 and 16 of the oestrous cycle and Day 24 of pregnancy (n = 3 pools/group) using Qiagen PCR arrays. A total of 16 miRNAs were differentially expressed (FDR < 0.1) in plasma between pregnant and non-pregnant animals. RT-qPCR validation using the same plasma samples confirmed that miR-26a was differentially upregulated on Day 16 pregnant relative to non-pregnant heifers (1.7-fold; P = 0.043), whereas miR-1249 tended to be upregulated in Day 16 pregnant heifers (1.6-fold; P = 0.081). Further validation in an independent group of heifers confirmed an increase in plasma miR-26a levels during early pregnancy, which was significant only on Day 24 (2.0-fold; P = 0.027). Through genome-wide analyses we have successfully profiled plasma miRNA populations associated with early pregnancy in cattle. We have identified miR-26a as a potential circulating biomarker of early pregnancy.

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Plasma samples from pregnant who developed preeclampsia and remained healthy along pregnancy (controls)

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