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Time course of maternal circulating miRNA signatures associated to normal human pregnancy

ABSTRACT: Emerging evidence has revealed alterations of microRNA (miRNA) profiles in peripheral blood associated to changes in a range of physiological conditions, suggesting that circulating miRNA profiles could be used as prognostic and/or diagnostic biomarkers for a wide variety of clinical conditions. Normal human pregnancy poses an extensive number of physiological challenges, affecting virtually every level of the pregnant woman’s biology, as well as changing contributions of the placenta and fetus. In this cohort study, using longitudinal large-scale profiling of circulating miRNAs at four defined stages during and after normal pregnancy, relative to non-pregnant controls, we investigate temporal changes in miRNA profiles as potential biomarkers of pregnancy evolution. By comparing the profiling of blood plasma miRNAs with available expression data, we found that miRNAs most prominently expressed in key reproductive tissues are collectively down regulated throughout pregnancy. Furthermore, we find a bias in the proportion of differentially expressed miRNAs associated with fetal sex right from the first trimester. Lastly, by combining circulating miRNAs expression with fetal growth indicators derived from the same women, we identify a robust miRNA signature associated to fetal growth during normal pregnancy. Our results demonstrate the existence of temporal changes of specific miRNAs associated to distinct aspects of pregnancy, including correlates of placental function, fetal gender, and fetal growth, as well as an early lactation related signature; strongly suggesting the potential of peripheral miRNAs as biomarkers of normal pregnancy.

ORGANISM(S): Homo sapiens

PROVIDER: GSE165740 | GEO | 2024/01/22

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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Time course of maternal circulating miRNA signatures associated to normal human pregnancy

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