MicroRNA Expression and Regulation in Mouse Uterus during Embryo Implantation*

MicroRNAs (miRNAs) are 21-24-nucleotide non-coding RNAs found in diverse organisms. Although hundreds of miRNAs have been cloned or predicted, only very few miRNAs have been functionally characterized. Embryo implantation is a crucial step in mammalian reproduction. Many genes have been shown to be significantly changed in mouse uterus during embryo implantation. However, miRNA expression profiles in the mouse uterus between implantation sites and inter-implantation sites are still unknown. In this study, miRNA microarray was used to examine differential expression of miRNAs in the mouse uterus between implantation sites and inter-implantation sites. Compared with inter-implantation sites, there were 8 up-regulated miR-NAs at implantation sites, which were confirmed by both Northern blot and in situ hybridization. miR-21 was highly expressed in the subluminal stromal cells at implantation sites on day 5 of pregnancy. Because miR-21 was not detected in mouse uterus during pseudopregnancy and under delayed implantation, miR-21 expression at implantation sites was regulated by active blastocysts. Furthermore, we showed that Reck was the target gene of miR-21. Our data suggest that miR-21 may play a key role during embryo implantation.

[1]  P. Yin,et al.  Differential expression of microRNA species in human uterine leiomyoma versus normal myometrium. , 2008, Fertility and sterility.

[2]  John J Rossi,et al.  MicroRNAs in Disease and Potential Therapeutic Applications. , 2007, Molecular therapy : the journal of the American Society of Gene Therapy.

[3]  Q. Pan,et al.  The expression profile of micro-RNA in endometrium and endometriosis and the influence of ovarian steroids on their expression. , 2007, Molecular human reproduction.

[4]  Phillip A. Sharp,et al.  miRNA Profiling of Naïve, Effector and Memory CD8 T Cells , 2007, PloS one.

[5]  V. Beneš,et al.  miChip: a microarray platform for expression profiling of microRNAs based on locked nucleic acid (LNA) oligonucleotide capture probes. , 2007, Methods.

[6]  S. Dey,et al.  MicroRNA regulation of cyclooxygenase-2 during embryo implantation , 2007, Proceedings of the National Academy of Sciences.

[7]  G. Gores,et al.  mir-29 regulates Mcl-1 protein expression and apoptosis , 2007, Oncogene.

[8]  David M. Thomas,et al.  RECK—a newly discovered inhibitor of metastasis with prognostic significance in multiple forms of cancer , 2007, Cancer and Metastasis Reviews.

[9]  J. Hackermüller,et al.  Interleukin-6 dependent survival of multiple myeloma cells involves the Stat3-mediated induction of microRNA-21 through a highly conserved enhancer. , 2007, Blood.

[10]  C. Sander,et al.  A Mammalian microRNA Expression Atlas Based on Small RNA Library Sequencing , 2007, Cell.

[11]  Shuomin Zhu,et al.  MicroRNA-21 Targets the Tumor Suppressor Gene Tropomyosin 1 (TPM1)* , 2007, Journal of Biological Chemistry.

[12]  Patricia Soteropoulos,et al.  A micro‐RNA signature associated with race, tumor size, and target gene activity in human uterine leiomyomas , 2007, Genes, chromosomes & cancer.

[13]  T. Patel,et al.  The MicroRNA let-7a Modulates Interleukin-6-dependent STAT-3 Survival Signaling in Malignant Human Cholangiocytes* , 2007, Journal of Biological Chemistry.

[14]  F. Tang,et al.  Maternal microRNAs are essential for mouse zygotic development. , 2007, Genes & development.

[15]  Francois Natt,et al.  A novel microarray approach reveals new tissue-specific signatures of known and predicted mammalian microRNAs , 2007, Nucleic acids research.

[16]  Peter T. McHale,et al.  Small Regulatory RNAs May Sharpen Spatial Expression Patterns , 2007, PLoS Comput. Biol..

[17]  Edwin Wang,et al.  Global analysis of microRNA target gene expression reveals that miRNA targets are lower expressed in mature mouse and Drosophila tissues than in the embryos , 2006, Nucleic acids research.

[18]  X. Agirre,et al.  Identification by Real-time PCR of 13 mature microRNAs differentially expressed in colorectal cancer and non-tumoral tissues , 2006, Molecular Cancer.

[19]  N. Rajewsky.  microRNA target predictions in animals , 2006, Nature Genetics.

[20]  Jan Krützfeldt,et al.  Strategies to determine the biological function of microRNAs , 2006, Nature Genetics.

[21]  A. Pasquinelli,et al.  The evolving role of microRNAs in animal gene expression. , 2006, BioEssays : news and reviews in molecular, cellular and developmental biology.

[22]  Xiaowei Wang,et al.  Systematic identification of microRNA functions by combining target prediction and expression profiling , 2006, Nucleic acids research.

[23]  Sudhansu K. Dey,et al.  Roadmap to embryo implantation: clues from mouse models , 2006, Nature Reviews Genetics.

[24]  George A. Calin,et al.  Mammalian microRNAs: a small world for fine-tuning gene expression , 2006, Mammalian Genome.

[25]  C. Croce,et al.  A microRNA expression signature of human solid tumors defines cancer gene targets , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[26]  Stijn van Dongen,et al.  miRBase: microRNA sequences, targets and gene nomenclature , 2005, Nucleic Acids Res..

[27]  C. Burge,et al.  The Widespread Impact of Mammalian MicroRNAs on mRNA Repression and Evolution , 2005, Science.

[28]  Y. Tamura,et al.  RECK-mediated suppression of tumor cell invasion is regulated by glycosylation in human tumor cell lines. , 2005, Cancer research.

[29]  D. Charnock-Jones,et al.  Inhibition of Stat3 activation in the endometrium prevents implantation: a nonsteroidal approach to contraception. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[30]  James R. Brown,et al.  A computational view of microRNAs and their targets. , 2005, Drug discovery today.

[31]  George E. Sandusky,et al.  Dicer Is Required for Embryonic Angiogenesis during Mouse Development* , 2005, Journal of Biological Chemistry.

[32]  D. Bartel,et al.  Microarray profiling of microRNAs reveals frequent coexpression with neighboring miRNAs and host genes. , 2005, RNA.

[33]  J. Castle,et al.  Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs , 2005, Nature.

[34]  A. Bradley,et al.  Identification of mammalian microRNA host genes and transcription units. , 2004, Genome research.

[35]  H. Wada,et al.  Expression of a novel matrix metalloproteinase regulator, RECK, and its clinical significance in resected non-small cell lung cancer. , 2004, European journal of cancer.

[36]  Jeff Reese,et al.  Molecular cues to implantation. , 2004, Endocrine reviews.

[37]  Michael Z Michael,et al.  Reduced accumulation of specific microRNAs in colorectal neoplasia. , 2003, Molecular cancer research : MCR.

[38]  K. Korach,et al.  Estrogen receptor-dependent genomic responses in the uterus mirror the biphasic physiological response to estrogen. , 2003, Molecular endocrinology.

[39]  F. DeMayo,et al.  A genomic approach to identify novel progesterone receptor regulated pathways in the uterus during implantation. , 2002, Molecular endocrinology.

[40]  Zeng-Ming Yang,et al.  Differential Expression of Microsomal Prostaglandin E Synthase at Implantation Sites and in Decidual Cells of Mouse Uterus1 , 2002, Biology of reproduction.

[41]  David B. Alexander,et al.  The Membrane-Anchored MMP Inhibitor RECK Is a Key Regulator of Extracellular Matrix Integrity and Angiogenesis , 2001, Cell.

[42]  S K Das,et al.  Global Gene Expression Analysis to Identify Molecular Markers of Uterine Receptivity and Embryo Implantation* 210 , 2001, The Journal of Biological Chemistry.

[43]  L. Lim,et al.  An Abundant Class of Tiny RNAs with Probable Regulatory Roles in Caenorhabditis elegans , 2001, Science.

[44]  W. Alvord,et al.  Dual control of LIF expression and LIF receptor function regulate Stat3 activation at the onset of uterine receptivity and embryo implantation , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[45]  W. Krause.  Computer-assisted semen analysis systems: comparison with routine evaluation and prognostic value in male fertility and assisted reproduction. , 1995, Human reproduction.

[46]  G. Schultz,et al.  Proteinase expression in early mouse embryos is regulated by leukaemia inhibitory factor and epidermal growth factor. , 1995, Development.

[47]  C. Stewart,et al.  Blastocyst implantation depends on maternal expression of leukaemia inhibitory factor , 1992, Nature.

[48]  Z. Werb,et al.  Metalloproteinases mediate extracellular matrix degradation by cells from mouse blastocyst outgrowths. , 1992, Development.

[49]  Z. Werb,et al.  92-kD type IV collagenase mediates invasion of human cytotrophoblasts , 1991, The Journal of cell biology.

[50]  R. Danner,et al.  Influence of IFN-on gene expression in normal human bronchial epithelial cells : modulation of IFN-effects by dexamethasone , 2005 .

[51]  H. M. Beier,et al.  Embryo-maternal signalling: how the embryo starts talking to its mother to accomplish implantation. , 2003, Reproductive biomedicine online.

[52]  S. Dey,et al.  Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in the mouse uterus during the peri-implantation period. , 1997, Developmental genetics.