| Title: |
The imprinted Igf2-Igf2r axis is critical for matching placental microvasculature expansion to fetal growth. |
| Authors: |
Sandovici, Ionel; Georgopoulou, Aikaterini; Pérez-García, Vicente; Hufnagel, Antonia; López-Tello, Jorge; Lam, Brian YH; Schiefer, Samira N; Gaudreau, Chelsea; Santos, Fátima; Hoelle, Katharina; Yeo, Giles SH; Burling, Keith; Reiterer, Moritz; Fowden, Abigail L; Burton, Graham J; Branco, Cristina M; Sferruzzi-Perri, Amanda N; Constância, Miguel |
| Publisher Information: |
Elsevier BV Department of Obstetrics And Gynaecology https://doi.org/10.1016/j.devcel.2021.12.005 Dev Cell 2021-12-09T00:31:11Z 2021-12-09T00:31:11Z 2022-01-10 2021-12-07T11:39:04Z |
| Document Type: |
Electronic Resource |
| Abstract: |
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 angiocrine effects of IGF2 on placental microvasculature expansion are mediated, in part, through IGF2R and angiopoietin-Tie2/TEK signaling. Additionally, IGF2 exerts IGF2R-ERK1/2-dependent pro-proliferative and angiogenic effects on primary feto-placental endothelial cells ex vivo. Endothelial and fetus-derived IGF2 also plays an important role in trophoblast morphogenesis, acting through Gcm1 and Synb. Thus, our study reveals a direct role for the imprinted Igf2-Igf2r 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.; This work was supported by Biotechnology and Biological Sciences Research Council (grant BB/H003312/1 to M.C.), Medical Research Council (MRC_MC_UU_12012/4 to M.C.; MRC_MC_UU_12012/5 to the MRC Metabolic Diseases Unit; MR/R022690/1 to A.N.S-P.), Spanish Ministry of Science and Innovation (RYC-2019-026956 and PID2020-114459RA-I00 to V.P-G.), Wellcome Trust (Sir Henry Wellcome Postdoctoral Fellowship 220456/Z/20/Z to J.L-T.), Royal Society (Dorothy Hodgkin Research Fellowship grant DH130036 to A.N.S-P.), Centre for Trophoblast Research and the NIHR Cambridge BRC Cell Phenotyping Hub. |
| Index Terms: |
IGF2; IGF2R; angiogenesis; angiopoietins; development; endothelial cells; fetal growth; genomic imprinting; placenta; trophoblast morphogenesis; Animals; Cell Line; DNA-Binding Proteins; Endothelial Cells; Female; Fetal Development; Fetus; Insulin-Like Growth Factor II; Mice; Mice, Inbred C57BL; Microvessels; Neovascularization, Physiologic; Placenta; Placentation; Pregnancy; Receptor, IGF Type 2; Transcription Factors; Trophoblasts; Article |
| URL: |
https://www.repository.cam.ac.uk/handle/1810/331286 |
| Availability: |
Open access content. Open access content; Attribution 4.0 International; https://creativecommons.org/licenses/by/4.0 |
| Note: |
application/pdf; application/pdf; application/vnd.openxmlformats-officedocument.spreadsheetml.sheet; application/vnd.openxmlformats-officedocument.spreadsheetml.sheet; application/vnd.openxmlformats-officedocument.spreadsheetml.sheet; English |
| Other Numbers: |
HS1 oai:www.repository.cam.ac.uk:1810/331286; 10.17863/CAM.78733; 1489035682 |
| Contributing Source: |
UNIV OF CAMBRIDGE; From OAIster®, provided by the OCLC Cooperative. |
| Accession Number: |
edsoai.on1489035682 |
| Database: |
OAIster |