title: MiR-145 suppresses embryo-epithelial juxtacrine communication at implantation by modulating maternal IGF1R.
abstract: Successful implantation requires the synchronization of viable embryonic development with endometrial receptivity. The mechanisms allowing for the initiation of crosstalk between the embryo and the endometrium remain elusive; however, recent studies have revealed that there are alterations in endometrial microRNAs (miRs) in women suffering repeated implantation failure and that one of the altered miRs is miR-145. We assessed the role of miR-145 and its target IGF1R, in early implantation. miR-145 overexpression and IGF1R knockdown were achieved in Ishikawa endometrial cells. Quantitative PCR, western blotting and 3'UTR luciferase reporter assays confirmed that IGF1R is a direct target of miR-145 in the endometrium. Attachment of mouse embryos or IGF1-coated beads to endometrial epithelial cells was used to study the effects of altered miR-145 and/or IGF1R expression on early implantation events. miR-145 overexpression or specific reduction of IGF1R impaired attachment in both cases. An IGF1R target protector prevented the miR-145-mediated reduction in IGF1R and reversed the effect of miR-145 overexpression on attachment. The data demonstrate that miR-145 influences embryo attachment by reducing the level of IGF1R in endometrium.
authors.affiliation: Maternal and Fetal Health Research Centre, Institute of Human Development, University of Manchester, Manchester M13 9WL, UK St Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester M13 9WL, UK Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Level 3, Women's Centre, John Radcliffe Hospital, Headington, Oxford OX3 9DU, UK.
authors.forename: Youn-Jung
authors.initials: YJ
authors.lastname: Kang
authors.affiliation: Maternal and Fetal Health Research Centre, Institute of Human Development, University of Manchester, Manchester M13 9WL, UK St Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester M13 9WL, UK.
authors.forename: Miranda
authors.initials: M
authors.lastname: Lees
authors.affiliation: Centre for Endocrinology & Diabetes, Institute of Human Development, University of Manchester, AV Hill Building, Oxford Road, Manchester, M13 9PT, UK.
authors.forename: Laura C
authors.initials: LC
authors.lastname: Matthews
authors.affiliation: Faculty of Life Sciences, Michael Smith Building, Oxford Road, Manchester, M13 9PT, UK.
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Kimber
authors.affiliation: Maternal and Fetal Health Research Centre, Institute of Human Development, University of Manchester, Manchester M13 9WL, UK St Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester M13 9WL, UK k.a.forbes@leeds.ac.uk john.aplin@manchester.ac.uk.
authors.forename: Karen
authors.initials: K
authors.lastname: Forbes
authors.affiliation: Maternal and Fetal Health Research Centre, Institute of Human Development, University of Manchester, Manchester M13 9WL, UK St Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester M13 9WL, UK k.a.forbes@leeds.ac.uk john.aplin@manchester.ac.uk.
authors.forename: John D
authors.initials: JD
authors.lastname: Aplin
mesh_terms: D000818:Animals; D002450:Cell Communication; D045744:Cell Line, Tumor; D046149:Embryo Culture Techniques; D010064:Embryo Implantation / Q000235:genetics / Q000502:physiology*; D004717:Endometrium / Q000378:metabolism / Q000502:physiology*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D008863:Microspheres; D034622:RNA Interference; D034741:RNA, Small Interfering; D017526:Receptor, IGF Type 1; D017451:Receptors, Somatomedin / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*
chemical_list: C000597236:IGF1R protein, human; C541010:MIRN145 microRNA, human; D035683:MicroRNAs; D034741:RNA, Small Interfering; D017451:Receptors, Somatomedin; D017526:Receptor, IGF Type 1
keywords: Embryo; Endometrium; IGF1R; Implantation; miR-145; miRNA