ArticleProceedings of the National Academy of Sciences of the United States of America2010
miR-200 family and targets, ZEB1 and ZEB2, modulate uterine quiescence and contractility during pregnancy and labor.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 143 papers, 1 of them a synthesis that pooled it.
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Who cites it
143 citing papers in PubMed, 1 synthesis or guideline pooled it, 288 citations in OpenAlex.
- A systematic review and meta-analysis of progestogen use for maintenance tocolysis after preterm labor in women with intact membranes.International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics · 2016Pooled it
- Maternal plasma miRNAs as biomarkers during mid-pregnancy to predict later spontaneous preterm birth: a pilot study.Scientific reports · 2017Trial
- Vaginal progesterone reduces the rate of preterm birth in women with a sonographic short cervix: a multicenter, randomized, double-blind, placebo-controlled trial.Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology · 2011Trial
- Derepression of a single microRNA target causes female infertility in mice.Nucleic acids research · 2026Article
- Multi-tissue miRNA networks in preterm birth: from molecular mechanisms to precision medicine.Frontiers in immunology · 2026Review
- Analyzing the relationship of RNA and DNA methylation with gene expression.Genome biology · 2025Article
- An Insight into Differentially Expressed Genes and MicroRNAs in the Pituitary Glands of the Two Estrous Phases of Sheep with DifferentAnimals : an open access journal from MDPI · 2025Article
- Review
- Prenatal maternal stress in rats alters the epigenetic and transcriptomic landscape of the maternal-fetal interface across four generations.Communications biology · 2025Article
- Regulation of term and preterm labor: genetics and epigenetics.Frontiers in genetics · 2025Article
- Microbial metabolites short chain fatty acids, tight junction, gap junction, and reproduction: a review.Frontiers in cell and developmental biology · 2025Review
- Perinatal Psychoneuroimmunology of Prenatal Stress and Its Effects on Fetal and Postnatal Brain Development.Methods in molecular biology (Clifton, N.J.) · 2025Article
- The Response of the miRNA Profiles of the Thyroid Gland to the Artificial Photoperiod in Ovariectomized and Estradiol-Treated Ewes.Animals : an open access journal from MDPI · 2024Article
- Decline in corepressor CNOT1 in the pregnant myometrium near term impairs progesterone receptor function and increases contractile gene expression.The Journal of biological chemistry · 2024Article
- The hormonal control of parturition.Physiological reviews · 2024Review
- A pivotal role for the IL-1β and the inflammasome in preterm labor.Scientific reports · 2024Article
- 20α-Hydroxysteroid Dehydrogenase Expression in the Human Myometrium at Term and Preterm Birth: Relationships to Fetal Sex and Maternal Body Mass Index.Reproductive sciences (Thousand Oaks, Calif.) · 2023Article
- Identification and characterization of circRNAs in peri-implantation endometrium between Yorkshire and Erhualian pigs.BMC genomics · 2023Article
- Role of Transcription Factors in the Management of Preterm Birth: Impact on Future Treatment Strategies.Reproductive sciences (Thousand Oaks, Calif.) · 2023Review
- MYB and ELF3 differentially modulate labor-inducing gene expression in myometrial cells.PloS one · 2023Article
83 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Throughout most of pregnancy, uterine quiescence is maintained by increased progesterone receptor (PR) transcriptional activity, whereas spontaneous labor is initiated/facilitated by a concerted series of biochemical events that activate inflammatory pathways and have a negative impact on PR function. In this study, we uncovered a previously undescribed regulatory pathway whereby micro-RNAs (miRNAs) serve as hormonally modulated and conserved mediators of contraction-associated genes in the pregnant uterus in the mouse and human. Using miRNA and gene expression microarray analyses of uterine tissues, we identified a conserved family of miRNAs, the miR-200 family, that is highly induced at term in both mice and humans as well as two coordinately down-regulated targets, zinc finger E-box binding homeobox proteins ZEB1 and ZEB2, which act as transcriptional repressors. We also observed up-regulation of the miR-200 family and down-regulation of ZEB1 and ZEB2 in two different mouse models of preterm labor. We further demonstrated that ZEB1 is directly up-regulated by the action of progesterone (P(4))/PR at the ZEB1 promoter. Excitingly, we observed that ZEB1 and ZEB2 inhibit expression of the contraction-associated genes, oxytocin receptor and connexin-43, and block oxytocin-induced contractility in human myometrial cells. Together, these findings implicate the miR-200 family and their targets, ZEB1 and ZEB2, as unique P(4)/PR-mediated regulators of uterine quiescence and contractility during pregnancy and labor and shed light on the molecular mechanisms involved in preterm birth.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.