Effect of labor on plasma concentrations and postpartum clearance of cell-free, pregnancy-associated, placenta-specific microRNAs

Morisaki, Shintaro; Miura, Kiyonori; Higashijima, Ai; Abe, Shuhei; Miura, Shoko; Hasegawa, Yoshihiro; Yoshida, Atsumi; Kaneuchi, Masanori; Yoshiura, Koh-ichiro; Masuzaki, Hiroaki

doi:10.1002/pd.4479

Cited by 16 publications

(16 citation statements)

References 26 publications

(65 reference statements)

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“…miRNA profiles in amniotic fluid reveal their involvement in pathways (such as axon guidance, focal adhesion, and mitogen-activated protein kinase signaling pathways) related to the normal development of the nervous system and other organs (Figure 1) [52]. Even though the effect of labour on miRNA profiles has been reported in plasma, miRNA profiles have yet to be identified in milk or amniotic fluid based on vaginal or caesarean-section modes of delivery [53]. The mode of delivery has been shown to affect the bacterial presence and abundance in human milk [54].…”

Section: New Kids On the Block: Mirnas Really Do Mattermentioning

confidence: 99%

Roles of MicroRNA across Prenatal and Postnatal Periods

Floris

Kraft

Altosaar

2016

IJMS

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Communication between mother and offspring in mammals starts at implantation via the maternal–placental–fetal axis, and continues postpartum via milk targeted to the intestinal mucosa. MicroRNAs (miRNAs), short, noncoding single-stranded RNAs, of about 22 nucleotides in length, are actively involved in many developmental and physiological processes. Here we highlight the role of miRNA in the dynamic signaling that guides infant development, starting from implantation of conceptus and persisting through the prenatal and postnatal periods. miRNAs in body fluids, particularly in amniotic fluid, umbilical cord blood, and breast milk may offer new opportunities to investigate physiological and/or pathological molecular mechanisms that portend to open novel research avenues for the identification of noninvasive biomarkers.

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Section: New Kids On the Block: Mirnas Really Do Mattermentioning

confidence: 99%

Roles of MicroRNA across Prenatal and Postnatal Periods

Floris

Kraft

Altosaar

2016

IJMS

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“…We have previously shown that placental weight is associated with circulating levels of maternal plasma cell-free pregnancy-associated, placentaspecific miRNAs 43 and that labor contraction significantly increases the circulating levels of pregnancy-associated, placenta-specific miRNAs (miR-515-3p, -517a, -517c, and -518b) in maternal plasma. 44 In this study, there was no significant difference in placental weight between the placental abruption and the uncomplicated pregnancy groups. Generally, uterine hypertonus or frequent uterine contractions are seen with placental abruption.…”

Section: Discussionmentioning

confidence: 76%

“…1 Therefore, in placenta abruption, it is possible that the circulating level of plasma cell-free miR-517c (from C19MC) is increased through communication between placental and maternal circulations following uterine contraction. 44 However, there were no significant differences in the maternal plasma levels of other pregnancy-associated, placenta-specific miRNAs (miR-515-3p, -517a, and -518b) between the placental abruption and uncomplicated pregnancy groups. Discrepancies in the plasma concentration of placenta-specific miRNAs within C19MC (increased levels of cell-free miR-517a and decreased levels of cell-free miR-518b) have also been reported in placenta previa pregnancy.…”

Section: Discussionmentioning

confidence: 95%

Circulating Levels of Pregnancy-Associated, Placenta-Specific microRNAs in Pregnant Women With Placental Abruption

et al. 2017

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The aim of this study was to clarify the association between circulating pregnancy-associated, placenta-specific microRNAs (miRNAs) in maternal plasma and placental abruption. All samples were obtained after receiving written informed consent, and the study protocol was approved by the institutional review board. Maternal blood samples (7 mL) were obtained at 25 to 40 weeks of gestation from 15 cases of placental abruption (placental abruption group) and from 24 cases of uncomplicated pregnancies (uncomplicated pregnancy group). The plasma concentrations of pregnancy-associated, placenta-specific miRNAs (miR-515-3p, -517a, -517c, and -518b) were measured by quantitative real-time reverse transcription-polymerase chain reaction. There were no significant differences in clinical characteristics between the 2 groups. The median concentration of plasma cell-free miR-517c in the placental abruption group was 21 672.2 copies/mL, whereas that in the uncomplicated pregnancy group was 13 452.0 copies/mL (Mann-Whitney U test, P = .047). Receiver operating characteristic curve analysis revealed that plasma cell-free miR-517c levels discriminated placental abruption from uncomplicated pregnancy with an area under the curve of 0.692. When a cutoff negative/positive value of 15 669.6 copies/mL was selected, the sensitivity and specificity were 73.3% and 62.5%, respectively. In addition, the positive and negative predictive values were 55.0% and 78.9%, respectively. Plasma cell-free miR-517a and miR-517c levels in the large abruption (degree of abruption ≥50% of placenta) group were significantly higher than in the small abruption (<50%) group ( P = .03 for both miRNAs). In conclusion, the circulating level of cell-free miR-517c in maternal plasma was increased as a consequence of placental abruption and may be a potential biomedical marker for placental abruption.

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“…[54][55][56] MicroRNAs have been shown to be very stable in the plasma samples for up to 24 h at room temperature 57,58 and rapidly cleared after the delivery, usually within 24 h after the delivery. 39,40,59,60 In this study, we showed that the degradation of the residual pre-malignant or malignant tissues is accompanied by the continuous decline of circulating C19MC microRNAs, and in case of complete remission of GTD/GTN, extracellular C19MC microRNAs are undetectable in patients' circulation similar as in the circulation of non-pregnant individuals. 39,40 Many cancer treatments work by causing cancer cells to enter an advanced stage of a process known as programmed cell death or apoptosis.…”

Section: Discussionmentioning

confidence: 88%

Follow-up of gestational trophoblastic disease/neoplasia via quantification of circulating nucleic acids of placental origin using C19MC microRNAs, hypermethylated RASSF1A, and SRY sequences

2017

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The aim of the study was to evaluate the effectiveness of placental-specific markers, extracellular fetal DNA (sexdetermining region Y and hypermethylated RASSF1A sequences) and circulating C19MC microRNAs (miR-516-5p, miR-517-5p, miR-518b, miR-520a-5p, miR-520h, miR-525, and miR-526a) for the diagnosis and consecutive follow-up of gestational trophoblastic disease/neoplasia. Increased levels of extracellular fetal DNA and C19MC microRNAs were detected in patients with active disease when compared with the period when the patients reached remission of the disease. The positive correlation between plasma levels of hypermethylated RASSF1A sequence, C19MC microRNAs, and human chorionic gonadotropin serum levels was found. MiR-520a-5p had the best performance to detect patients with active disease (a positive predictive value of 100% at a null false positive ratio (FPR)). MiR-516-5p and miR-525 were able to diagnose 100% of women with active disease at the FPR 3.9%/7.7%. The overall predictive capacity of single miR-526a (81.8% at null FPR), miR-517-5p (90.9% at 15.4% FPR), miR-518b (100% at 38.5% FPR), and miR-520h (90.9% at 26.9% FPR) biomarkers to detect active disease cases was slightly lower. Transient increase in C19MC microRNA plasma levels after the first cycle of chemotherapy indicated the decay of placental trophoblast residual tissue. The increased levels of extracellular fetal DNA and placental-specific C19MC microRNAs are associated with gestational trophoblastic disease/neoplasia. Screening of extracellular placental-specific biomarkers may represent an additional option to identify a significant proportion of women with active disease and to monitor the therapy response. Non-invasive follow-up of the decomposing residual tissue in the form of extracellular nucleic acids of placental origin packed into apoptotic bodies derived from placental trophoblasts is available.

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Effect of labor on plasma concentrations and postpartum clearance of cell-free, pregnancy-associated, placenta-specific microRNAs

Abstract: The presence of labor affects cell-free, pregnancy-associated, placenta-specific miRNA levels in maternal plasma. Labor also affects postpartum clearance of these miRNAs 24 h after delivery.

Cited by 16 publications

References 26 publications

Roles of MicroRNA across Prenatal and Postnatal Periods

Roles of MicroRNA across Prenatal and Postnatal Periods

Circulating Levels of Pregnancy-Associated, Placenta-Specific microRNAs in Pregnant Women With Placental Abruption

Follow-up of gestational trophoblastic disease/neoplasia via quantification of circulating nucleic acids of placental origin using C19MC microRNAs, hypermethylated RASSF1A, and SRY sequences

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