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| Status |
Public on Oct 30, 2010 |
| Title |
The miR-200 family and targets, ZEB1 and ZEB2, modulate uterine quiescence and contractility during pregnancy and labor |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Throughout most of pregnancy, uterine quiescence is maintained by increased progesterone receptor (PR) transcriptional activity, while spontaneous labor is initiated/facilitated by a concerted series of biochemical events that activate inflammatory pathways and negatively impact PR function. In this study, we uncovered a new regulatory pathway whereby miRNAs serve as hormonally-modulated and conserved mediators of contraction-associated genes in the pregnant uterus from mouse to 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 downregulated targets, zinc finger E-box binding homeobox proteins, ZEB1 and ZEB2, which act as transcriptional repressors. We also observed upregulation of the miR-200 family and downregulation of ZEB1 and ZEB2 in two different mouse models of preterm labor. We further demonstrated that ZEB1 is directly upregulated by the action of P4/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 novel progesterone/PR- mediated regulators of uterine quiescence and contractility during pregnancy and labor, and shed new light on the molecular mechanisms involved in preterm birth.
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| Overall design |
RNA was purified from mouse myometrium (miRNeasy kit, Qiagen). miRNA microarray was performed (LC Sciences) on 18 biological replicates of murine myometrium at 15.5 dpc and an equal number of replicates at 18.5 dpc. Gene expression microarray assays were performed (UT Southwestern Medical Center) on the same 36 samples as detailed further in SI Materials and Methods.
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| Contributor(s) |
Renthal NE, Chen CC, Williams CK, Gerard RD, Prange-Kiel J, Mendelson CR |
| Citation(s) |
21079000 |
| Submission date |
Oct 29, 2010 |
| Last update date |
Jan 16, 2019 |
| Contact name |
Carole R Mendelson |
| E-mail(s) |
carole.mendelson@utsouthwestern.edu
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| Phone |
214-648-2944
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| Organization name |
University of Texas Southwestern Medical Center
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| Department |
Biochemistry
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| Street address |
5323 Harry Hines Blvs
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| City |
Dallas |
| State/province |
TX |
| ZIP/Postal code |
75390-9038 |
| Country |
USA |
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| Platforms (1) |
| GPL6887 |
Illumina MouseWG-6 v2.0 expression beadchip |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA134385 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE25017_2009_03_04_Nora_110608_ExpProfile_FDR.txt.gz |
6.9 Mb |
(ftp)(http) |
TXT |
| GSE25017_RAW.tar |
15.8 Mb |
(http)(custom) |
TAR |
| GSE25017_non-normalized.txt.gz |
1.9 Mb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
| Processed data are available on Series record |
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