Expression patterns of microRNAs in the chorioamniotic membranes: a role for microRNAs in human pregnancy and parturition (original) (raw)
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American Journal of Obstetrics and Gynecology, 2007
The aim of this study was to identify differential expression of microRNAs (miRNAs) in chorioamniotic membranes with advancing gestation, labor, and inflammation. STUDY DESIGN: Expression profiles of 157 miRNAs in the chorioamniotic membranes were obtained from patients in the following groups: 1) term not in labor (n ϭ 10); 2) term in labor (n ϭ 10); 3) preterm labor with histologic chorioamionitis (n ϭ 9); and 4) without histologic chorioamnionitis (n ϭ 10).
2007
The aim of this study was to identify differential expression of microRNAs (miRNAs) in chorioamniotic membranes with advancing gestation, labor, and inflammation. STUDY DESIGN: Expression profiles of 157 miRNAs in the chorioamniotic membranes were obtained from patients in the following groups: 1) term not in labor (n ϭ 10); 2) term in labor (n ϭ 10); 3) preterm labor with histologic chorioamionitis (n ϭ 9); and 4) without histologic chorioamnionitis (n ϭ 10).
PLoS ONE, 2011
Background: The human amnion plays a pivotal role in parturition. Two of its compartments, the placental amnion and the reflected amnion, have distinct transcriptome and are functionally coordinated for parturition. This study was conducted to determine the microRNA (miRNA) expression pattern and its significance in the placental amnion and the reflected amnion in association with labor at term. Methodology/Principal Findings: MicroRNA microarray, real-time quantitative RT-PCR (qRT-PCR), and miRNA in situ hybridization analyses of the placental amnion and the reflected amnion (n = 20) obtained at term were conducted. Luciferase assay, transfection, and qRT-PCR analyses of primary amnion epithelial cells (AECs) and amnion mesenchymal cells (AMCs) were performed. MicroRNA microarray analysis demonstrated differential expression of 32 miRNAs between the placental amnion and the reflected amnion after labor. Thirty-one (97%) miRNAs, which included miR-143 and miR-145, a cardiovascular-specific miRNA cluster, were down-regulated in the reflected amnion. Analyses of miR-143 and miR-145 by qRT-PCR confirmed microarray results, and further demonstrated their decreased expression in the reflected amnion with labor. Interestingly, expression of miR-143 and miR-145 was higher in AMCs than in AECs (p,0.05). Luciferase assay and transfection confirmed miR-143 binding to 39 UTR of prostaglandin-endoperoxidase synthase 2 (PTGS2) mRNA and miR-143 regulation of PTGS2 in AMCs. Conclusions: We report region-specific amniotic microRNAome and miR-143 regulation of PTGS2 in the context of human labor at term for the first time. The findings indicate that miRNA-mediated post-transcriptional regulation of gene expression machinery in the amnion plays an important role in the compartments (placental amnion vs reflected amnion) and in a cell type-specific manner (AECs vs AMCs) for parturition.
Expression levels of maternal plasma microRNAs in preeclamptic pregnancies
Journal of Obstetrics and Gynaecology, 2020
The present study aimed to identify the differential expression profiles of microRNAs in the plasma between patients with preeclampsia (PE) and healthy pregnancies using quantitative real-time PCR. The expression profiles of 32 miRNAs in maternal plasma from 31 patients with PE and 32 healthy pregnancies were evaluated. The expression levels of eight miRNAs including miR-210, miR-375, miR-197-3p, miR-132-3p, miR-29a-3p, miR-328, miR-24-3p, and miR-218-5p were significantly upregulated and the expression levels of three miRNAs, including miR-302b-3p, miR-191-5p, and miR-17-5p, were significantly downregulated in patients with preeclampsia when compared to healthy pregnant women. In conclusion, we identified 11 miRNAs that may be potential biomarkers for non-invasive diagnosis and a pivotal role in the prediction of PE. Considering the small cohort of patients, further studies with larger samples from different gestational stages are necessary to confirm our findings. IMPACT STATEMENT What is already known on this subject? The alterations in the release pattern of placenta-specific miRNAs detected in maternal serum have been found to be associated with pregnancy-related complications such as preeclampsia (PE). What do the results of this study add? In the present study, the release pattern of seven miRNAs had consistency and two of them had inconsistency with previous researches. Moreover, two novel miRNAs were also defined to demonstrate the interrelationship between PE and miRNAs. What are the implications of these findings for clinical practice and/or future research? The identification of 11 miRNAs that may be potential biomarkers for non-invasive diagnosis and a pivotal role in the prediction of PE. Considering the small cohort of patients, further studies with larger samples from different gestational stages are necessary to confirm our findings.
Distinct cervical microRNA profiles are present in women destined to have a preterm birth
American Journal of Obstetrics and Gynecology, 2014
Although premature cervical remodeling is involved in preterm birth (PTB), the molecular pathways that are involved have not been elucidated fully. MicroRNAs (miRNAs) that are highly conserved single-stranded noncoding RNAs that play a crucial role in gene regulation have now been identified as important players in disease states. The objective of this study was to determine whether miRNA profiles in cervical cells are different in women who are destined to have a PTB compared with a term birth. STUDY DESIGN: A nested case-control study was performed. With the use of a noninvasive method, cervical cells were obtained at 2 time points in pregnancy. The cervical cell miRNA expression profiles were compared between women who ultimately had a PTB (n ¼ 10) compared with a term birth (n ¼ 10). MiRNA expression profiles were created with the Affymetrix GeneChip miRNA Array. The data were analyzed with the Significance of Analysis of Microarrays and Principle Components Analyses. A false-discovery rate of 20% was used to determine the most differentially expressed miRNAs. Validation was performed with quantitative polymerase chain reaction. In vitro studies were performed to confirm expression and regulation of select miRNAs. RESULTS: With a false-discovery rate of 20% of the 5640 miRNAs that were analyzed on the array, 99 miRNAs differed between those with a PTB vs a term birth. Qualitative polymerase chain reaction validated the array findings. In vitro studies confirmed expression of select miRNAs in cervical cells. CONCLUSION: MiRNA profiles in cervical cells may distinguish women who are at risk for PTB months before the outcome. With the large downstream effects of miRNAs on gene expression, these studies provide a new understanding of the processes that are involved in premature cervical remodeling and allow for the discovery of new therapeutic targets.
International Journal of Molecular Sciences, 2021
This prospective cross-sectional case-control study investigated the postpartal gene expression of microRNAs associated with diabetes/cardiovascular/cerebrovascular diseases in the peripheral white blood cells of women with anamnesis of preterm prelabor rupture of membranes (n = 58), spontaneous preterm birth (n = 55), and term delivery (n = 89) by a quantitative reverse transcription polymerase chain reaction. After pregnancies complicated by preterm prelabor rupture of membranes or spontaneous preterm birth, mothers showed diverse expression profiles for 25 out of 29 tested microRNAs (miR-1-3p, miR-16-5p, miR-17-5p, miR-20a-5p, miR-20b-5p, miR-21-5p, miR-23a-3p, miR-24-3p, miR-26a-5p, miR-29a-3p, miR-100-5p, miR-103a-3p, miR-125b-5p, miR-126-3p, miR-130b-3p, miR-133a-3p, miR-143-3p, miR-145-5p, miR-146a-5p, miR-181a-5p, miR-195-5p, miR-199a-5p, miR-221-3p, miR-499a-5p, and miR-574-3p). The earliest gestational ages at delivery and the lowest birth weights of newborns were associat...
Overexpression of miR-21 and miR-122 in preeclamptic placentas
Neuro endocrinology letters, 2015
Preeclampsia is a pregnancy-associated disease with the impact of genetic, epigenetic and environmental factors. Increased apoptosis was observed in cells from preeclamptic placentas. MicroRNAs are involved in the regulation of apoptosis and are abundant in placenta. In this study, we focused on the analysis of differential gene expression of apoptosis-associated miRNAs in preeclamptic placenta samples compared to the samples obtained from healthy pregnant women. MicroRNA was extracted from placental samples of patients with preeclampsia and physiological course of the pregnancy. The gene expression of miR-155, miR-122 and miR-21 in placenta and control samples was estimated by relative quantitation (RQ) using TaqMan probes, normalized against RNU44. The RQ mean values were statistically evaluated by Man-Whitney test. Using the relative gene expression analysis, we could observe a significant increase in gene expression of miR-155 (p<0.001), miR-21 (p<0.0001) and miR-122 (p<...
American Journal of Obstetrics and Gynecology, 2007
OBJECTIVE: Preeclampsia and small-for-gestational age (SGA) neonates have partially overlapping clinicopathologic features. Mi-croRNAs (miRNAs) are critical posttranscriptional regulators of gene expression. This study was performed to determine whether preeclampsia and SGA are associated with alterations in placental miRNA expression. STUDY DESIGN: Placentas were obtained from patients with (1) preeclampsia (n ϭ 9); (2) SGA (n ϭ 9); (3) preeclampsia ϩ SGA (n ϭ 9); and (4) a control group with spontaneous preterm labor and delivery (PTL; n ϭ 9). The expression of 157 miRNAs was assessed by real-time quantitative reverse transcription-polymerase chain reaction.
2020
Human parturition is a complicated biological process and the molecular mechanisms regulating the onset of labor are not well understood. Several studies propose that gene variants, proteins and miRNAs play a major role in maintaining pregnancy and aberrations in protein and miRNA levels may lead to pregnancy complications. The levels of proteins and miRNAs could prove to be useful biomarkers for monitoring the onset of labor. In this study, using proteomics and a genome analysis, we identified Calcineurin-like phosphoesterase domain-containing protein (CPPED1), as a potential biomarker of labor. CPPED1 was found to be downregulated in spontaneous term placentas compared with placentas from elective deliveries. The siRNA knockdown of CPPED1 in trophoblasts derived cells mostly affects pathways related to inflammation and angiogenesis, and these functions may be involved in the induction of labor or in maintaining pregnancy. In bladder cancer cells, CPPED1 has been shown to dephosphorylate AKT1 on the Ser-473 residue and to promote apoptosis via the AKT/PI3K pathway. In our studies using cells of placental origin AKT1 phosphorylation levels were unaffected by CPPED1 expression, whereas its silencing led to the upregulation of negative regulators of the PI3K pathway. In a comparative miRNAomics screen of spontaneous term vs. elective term placentas, we identified 54 differentially expressed miRNAs, out of which 23 miRNAs were upregulated and 31 were downregulated by at least 1.5-fold. Among the upregulated miRNAs, miRNA-371a-5p targets CPPED1 and posttranscriptionally regulates its expression by binding to its 3'UTR region. In addition, we found that CPPED1 and miR-371a-5p levels inversely correlate with each other in spontaneous and elective term placentas. Measuring the levels of CPPED1 and miR-371a-5p levels in maternal blood could be a potential diagnostic biomarker for labor. In order to elucidate the functions of CPPED1 we used a protein microarray to identify proteins that interact with CPPED1 in vitro and obtained a list of 36 proteins that potentially bind CPPED1. The interaction of CPPED1 with PAK4 and PIK3R2 was confirmed by co-immunoprecipitation and investigation of the cellular localization by BiFC studies showed that CPPED1 and PAK4 are colocalized in the cytoplasm, whereas CPPED1-PIK3R2 complex on the cell membrane. Further, by a mass spectrometry analysis, we found that CPPED1 dephosphorylates PAK4 on five different serine residues. The functional importance of these phosphorylation sites is still unknown. PIK3R2 phosphorylation was unaffected by CPPED1. Based on our studies we propose that the levels of CPPED1 and miRNA-371a-5p in the maternal circulation could serve as biomarkers for the prediction of labor. The functional role of CPPED1 on PIK3R2 and PAK4 remains to be studied.