Pregnancy-associated microRNAs in plasma as potential molecular markers of ectopic pregnancy

Miura, Kiyonori; Higashijima, Ai; Mishima, Hiroyuki; Miura, Shoko; Kitajima, Michio; Kaneuchi, Masanori; Yoshiura, Koh-ichiro; Masuzaki, Hiroaki

doi:10.1016/j.fertnstert.2015.01.041

Cited by 32 publications

(29 citation statements)

References 24 publications

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“…Levels of serum and plasma miR-141-3p have been reported by multiple studies to be significantly upregulated in serum and plasma samples of pregnant women using PCR-based miRNA arrays [11, 56], and as such, serves as an ideal candidate for validating the reference normalisation panel. The results presented here showed that significant changes in miR-141-3p expression between non-pregnant (with or without oral contraceptives) and pregnant females can be observed when the RT-qPCR data was normalised to the synthetic spike-ins.…”

Section: Discussionmentioning

confidence: 99%

“…It is vital, therefore, that suitable endogenous miRNAs are established in the appropriate study cohorts. In addition, there have been many studies which characterised miRNA expression profiles associated with pregnancy complications such as preeclampsia [62, 63], ectopic pregnancies [56] and gestational diabetes [64]. Baseline levels, however, are absent as these studies compared expression profiles between pregnant women only and not against non-pregnant participants.…”

Section: Discussionmentioning

confidence: 99%

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Identification of reference miRNAs in plasma useful for the study of oestrogen-responsive miRNAs associated with acquired Protein S deficiency in pregnancy

et al. 2017

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BackgroundAccumulating evidence indicate that circulating microRNAs (miRNAs) are useful independent non-invasive biomarkers, with unique miRNA signatures defined for various pathophysiological conditions. However, there are no established universal housekeeping miRNAs for the normalisation of miRNAs in body fluids. We have previously identified an oestrogen-responsive miRNA, miR-494, in regulating the anticoagulant, Protein S, in HuH-7 liver cells. Moreover, increased thrombotic risk associated with elevated circulating oestrogen levels is frequently observed in pregnant women and oral contraceptive users. In order to identify other oestrogen-responsive miRNAs, including miR-494, that may be indicative of increased thrombotic risk in plasma, we used nanoString analysis to identify robust and stable endogenous reference miRNAs for the study of oestrogen-responsive miRNAs in plasma.ResultsWe compared the plasma miRNA expression profile of individuals with: (1) Low circulating oestrogens (healthy men and non-pregnant women not taking oral contraceptives), (2) High circulating synthetic oestrogens, (women taking oral contraceptives) and (3) High circulating natural oestrogens (pregnant females >14 weeks gestation). From the nanoString analyses, 11 candidate reference miRNAs which exhibited high counts and not significantly differentially expressed between groups were selected for validation using realtime quantitative polymerase chain reaction (RT-qPCR) and digital droplet PCR (DDPCR) in pooled plasma samples, and the stability of their expression evaluated using NormFinder and BestKeeper algorithms. Four miRNAs (miR-25-5p, miR-188-5p, miR-222-3p and miR-520f) demonstrated detectable stable expression between groups and were further analysed by RT-qPCR in individual plasma samples, where miR-188-5p and miR-222-3p expression were identified as a stable pair of reference genes. The miRNA reference panel consisting of synthetic spike-ins cel-miR-39 and ath-miR159a, and reference miRNAs, miR-188-5p and miR-222-3p was useful in evaluating fold-change of the pregnancy-associated miRNA, miR-141-3p, between groups.ConclusionThe miRNA reference panel will be useful for normalising qPCR data comparing miRNA expression between men and women, non-pregnant and pregnant females, and the potential effects of endogenous and synthetic oestrogens on plasma miRNA expression.Electronic supplementary materialThe online version of this article (doi:10.1186/s13104-017-2636-3) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Identification of reference miRNAs in plasma useful for the study of oestrogen-responsive miRNAs associated with acquired Protein S deficiency in pregnancy

et al. 2017

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“…However, these biomarkers are primarily produced after 7 weeks of gestation and their clinical applicability is limited . More recently, plasma concentrations of cell‐free pregnancy‐associated microRNAs (miRNAs) have been evaluated in ectopic pregnancy and found to show a different distribution pattern compared to viable intrauterine pregnancy …”

Section: Other Biomarkersmentioning

confidence: 99%

Diagnostic Biomarkers for Predicting Adverse Early Pregnancy Outcomes

Memtsa¹,

Jauniaux²,

Gynaecologists³

2018

BJOG

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“…An aspect of placental miRNA signaling that makes these epigenetic regulators particularly intriguing in early life programming research is their ability to be detected in maternal blood (Chim et al, 2008), making them potential biomarkers for complications such as preeclampsia and ectopic pregnancy (Gunel et al, 2011; Miura et al, 2015; Zhao et al, 2013, 2012), as well as one day potentially for other maternal or fetal insults predictive of risk for neurodevelopmental disorders, such as autism spectrum disorders which have recently been associated with preeclampsic pregnancies (Walker et al, 2015). Although blood is rich in RNAses, miRNAs can travel through the maternal bloodstream complexed with Argonaute2 (Ago2), a key component of the RISC complex, or within extracellular vesicles termed exosomes providing protection from degradation (Arroyo et al, 2011; Fevrier and Raposo, 2004).…”

Section: Epigenetics: Energy Availability and Long-term Programmingmentioning

confidence: 99%

The omniscient placenta: Metabolic and epigenetic regulation of fetal programming

Nugent

Bale

2015

Frontiers in Neuroendocrinology

182

143

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Fetal development could be considered a sensitive period wherein exogenous insults and changes to the maternal milieu can have long-term impacts on developmental programming. The placenta provides the fetus with protection and necessary nutrients for growth, and responds to maternal cues and changes in nutrient signaling through multiple epigenetic mechanisms. The X-linked enzyme O-linked-N-acetylglucosamine transferase (OGT) acts as a nutrient sensor that modifies numerous proteins to alter various cellular signals, including major epigenetic processes. This review describes epigenetic alterations in the placenta in response to insults during pregnancy, the potential links of OGT as a nutrient sensor to placental epigenetics, and the implications of placental epigenetics in long-term neurodevelopmental programming. We describe the role of placental OGT in the sex-specific programming of hypothalamic-pituitary-adrenal (HPA) axis programming deficits by early prenatal stress as an example of how placental signaling can have long-term effects on neurodevelopment.

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Pregnancy-associated microRNAs in plasma as potential molecular markers of ectopic pregnancy

Cited by 32 publications

References 24 publications

Identification of reference miRNAs in plasma useful for the study of oestrogen-responsive miRNAs associated with acquired Protein S deficiency in pregnancy

Identification of reference miRNAs in plasma useful for the study of oestrogen-responsive miRNAs associated with acquired Protein S deficiency in pregnancy

Diagnostic Biomarkers for Predicting Adverse Early Pregnancy Outcomes

The omniscient placenta: Metabolic and epigenetic regulation of fetal programming

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