{"doi":"10.1101/520536","title":"The Imprinted\n                  <i>Igf2</i>\n                  -\n                  <i>Igf2r</i>\n                  Axis is Critical for Matching Placental Microvasculature Expansion to Fetal Growth","abstract":"<jats:title>SUMMARY</jats:title>\n                <jats:p>\n                  In all eutherian mammals, growth of the fetus is dependent upon a functional placenta, but whether and how the latter adapts to putative fetal signals is currently unknown. Here we demonstrate, through fetal, endothelial, hematopoietic and trophoblast-specific genetic manipulations in the mouse, that endothelial and fetus-derived IGF2 is required for the continuous expansion of the feto-placental microvasculature in late pregnancy. The effects of IGF2 on placental microvasculature expansion are mediated, in part, through IGF2R and angiopoietin-Tie2/TEK signalling. Additionally, IGF2 exerts IGF2R-ERK1/2-dependent pro-proliferative and angiogenic effects on primary feto-placental endothelial cells\n                  <jats:italic>ex vivo</jats:italic>\n                  . Endothelial and fetus-derived IGF2 also plays an important role in trophoblast morphogenesis, acting through\n                  <jats:italic>Gcm1</jats:italic>\n                  and\n                  <jats:italic>Synb</jats:italic>\n                  . Thus, our study reveals a direct role for the imprinted\n                  <jats:italic>Igf2-Igf2r</jats:italic>\n                  axis on matching placental development to fetal growth and establishes the principle that hormone-like signals from the fetus play important roles in controlling placental microvasculature and trophoblast morphogenesis.\n                </jats:p>","journal":null,"year":null,"id":660032,"datarank":0.29188652235829704,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"self_citation_contribution":0.29188652235829704,"citation_network_contribution":0.0,"self_endowment_contribution":0.29188652235829704,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1722959,"name":"Aikaterini Georgopoulou","orcid":null,"position":1,"is_corresponding":false},{"id":1722960,"name":"Vicente Pérez-García","orcid":null,"position":2,"is_corresponding":false},{"id":1722961,"name":"Antonia Hufnagel","orcid":"0000-0002-7030-4419","position":3,"is_corresponding":false},{"id":345335,"name":"Jorge López‐Tello","orcid":"0000-0002-7886-0233","position":4,"is_corresponding":false},{"id":355554,"name":"Brian Lam","orcid":"0000-0002-3638-9025","position":5,"is_corresponding":false},{"id":1722964,"name":"Samira N. Schiefer","orcid":null,"position":6,"is_corresponding":false},{"id":1722966,"name":"Chelsea Gaudreau","orcid":null,"position":7,"is_corresponding":false},{"id":1722968,"name":"Fátima Santos","orcid":"0000-0002-6516-6189","position":8,"is_corresponding":false},{"id":1722969,"name":"Katharina Hoelle","orcid":null,"position":9,"is_corresponding":false},{"id":614545,"name":"Giles S.H. Yeo","orcid":"0000-0001-8823-3615","position":10,"is_corresponding":false},{"id":639014,"name":"Keith Burling","orcid":"0000-0002-0109-7751","position":11,"is_corresponding":false},{"id":623443,"name":"Moritz Reiterer","orcid":"0000-0001-6943-9490","position":12,"is_corresponding":false},{"id":473168,"name":"Abigail L. Fowden","orcid":"0000-0002-3384-4467","position":13,"is_corresponding":false},{"id":511091,"name":"Graham J. Burton","orcid":"0000-0001-8677-4143","position":14,"is_corresponding":false},{"id":1263008,"name":"Cristina Branco","orcid":"0000-0001-6953-4922","position":15,"is_corresponding":false},{"id":345334,"name":"Amanda N. Sferruzzi‐Perri","orcid":"0000-0002-4931-4233","position":16,"is_corresponding":false},{"id":1043217,"name":"Miguel Constância","orcid":"0000-0002-8976-1679","position":17,"is_corresponding":false},{"id":1043216,"name":"Ionel Sandovici","orcid":"0000-0001-5674-4269","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"The Imprinted\n                  <i>Igf2</i>\n                  -\n                  <i>Igf2r</i>\n                  Axis is Critical for Matching Placental Microvasculature Expansion to Fetal Growth","abstract":"<jats:title>SUMMARY</jats:title>\n                <jats:p>\n                  In all eutherian mammals, growth of the fetus is dependent upon a functional placenta, but whether and how the latter adapts to putative fetal signals is currently unknown. Here we demonstrate, through fetal, endothelial, hematopoietic and trophoblast-specific genetic manipulations in the mouse, that endothelial and fetus-derived IGF2 is required for the continuous expansion of the feto-placental microvasculature in late pregnancy. The effects of IGF2 on placental microvasculature expansion are mediated, in part, through IGF2R and angiopoietin-Tie2/TEK signalling. Additionally, IGF2 exerts IGF2R-ERK1/2-dependent pro-proliferative and angiogenic effects on primary feto-placental endothelial cells\n                  <jats:italic>ex vivo</jats:italic>\n                  . Endothelial and fetus-derived IGF2 also plays an important role in trophoblast morphogenesis, acting through\n                  <jats:italic>Gcm1</jats:italic>\n                  and\n                  <jats:italic>Synb</jats:italic>\n                  . Thus, our study reveals a direct role for the imprinted\n                  <jats:italic>Igf2-Igf2r</jats:italic>\n                  axis on matching placental development to fetal growth and establishes the principle that hormone-like signals from the fetus play important roles in controlling placental microvasculature and trophoblast morphogenesis.\n                </jats:p>","is_dataset_classified":null,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"19162232","pmcid":null,"openalex_id":"https://openalex.org/W2910739516","authors":[],"funders":[{"funder_name":"UK Research and Innovation","grant_id":"BB/H003312/1","title":"Role of the imprinted Igf2 gene in pancreatic development and function"},{"funder_name":"Wellcome Trust","grant_id":"220456","title":"Determining the role of placental endocrine function in the development of gestational diabetes mellitus and its maternal metabolic long-term health consequences"},{"funder_name":"UK Research and Innovation","grant_id":"MR/R022690/1","title":"Biomarkers of materno-fetal health: role placental endocrine mediators in normal and obese pregnancies"}],"total_grants":3,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[{"year":2019,"count":1},{"year":2020,"count":2},{"year":2021,"count":3}],"oa_status":"green","license":"other-oa","oa_locations":[{"url":"https://pure.qub.ac.uk/en/publications/adcd151b-0538-48f6-972c-c44c3a57ae68","host_type":"repository"},{"url":"https://www.biorxiv.org/content/biorxiv/early/2019/01/16/520536.full.pdf","host_type":"repository"},{"url":"https://syndication.highwire.org/content/doi/10.1101/520536","host_type":"publisher"},{"url":"https://www.biorxiv.org/content/10.1101/520536v1","host_type":"repository"},{"url":"https://doi.org/10.1101/520536","host_type":""},{"url":"https://doi.org/10.1016/j.devcel.2021.12.005","host_type":""},{"url":"http://www.cell.com/article/S1534580721009941/pdf","host_type":""},{"url":"https://dx.doi.org/10.17863/cam.78733","host_type":""},{"url":"https://pubmed.ncbi.nlm.nih.gov/34963058","host_type":""},{"url":"http://dx.doi.org/10.1016/j.devcel.2021.12.005","host_type":""},{"url":"https://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=3874","host_type":""},{"url":"https://dx.doi.org/10.1101/520536","host_type":""},{"url":"https://pureadmin.qub.ac.uk/ws/files/292373047/1_s2.0_S1534580721009941_main.pdf","host_type":""},{"url":"https://pure.qub.ac.uk/en/publications/41949e0a-a30f-40be-8b50-59727c33304d","host_type":""},{"url":"https://doi.org/https://doi.org/10.1016/j.devcel.2021.12.005","host_type":""}],"fields_of_study":["Pregnancy and preeclampsia studies","Birth, Development, and Health","Growth Hormone and Insulin-like Growth Factors","0301 basic medicine","03 medical and health sciences","0303 health sciences"],"mesh_terms":[],"keywords":["Trophoblast","Fetus","Placenta","Biology","Placental Circulation","Morphogenesis","Cell biology","Andrology","Pregnancy","Medicine","Genetics","Gene","570","trophoblast morphogenesis","610","Neovascularization, Physiologic","IGF2R","Article","Receptor, IGF Type 2","Cell Line","Fetal Development","angiogenesis","Mice","Insulin-Like Growth Factor II","Animals","development","IGF2","Endothelial Cells","Placentation","genomic imprinting","Trophoblasts","DNA-Binding Proteins","Mice, Inbred C57BL","IGF2, IGF2R, angiogenesis, angiopoietins, development, endothelial cells, fetal growth, genomic imprinting, placenta, trophoblast morphogenesis","Microvessels","Female","angiopoietins","fetal growth","Transcription Factors"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-12T08:15:15.738636Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}