RT Journal Article SR Electronic T1 Fetus-derived IGF2 matches placental development to fetal demand JF bioRxiv FD Cold Spring Harbor Laboratory SP 520536 DO 10.1101/520536 A1 Sandovici, Ionel A1 Georgopoulou, Aikaterini A1 Hufnagel, Antonia S. A1 Schiefer, Samira N. A1 Santos, Fátima A1 Hoelle, Katharina A1 Lam, Brian Y.H. A1 Yeo, Giles S.H. A1 Burling, Keith A1 López-Tello, Jorge A1 Reiterer, Moritz A1 Fowden, Abigail L. A1 Burton, Graham J. A1 Sferruzzi-Perri, Amanda N. A1 Branco, Cristina M. A1 Constância, Miguel YR 2019 UL http://biorxiv.org/content/early/2019/01/16/520536.abstract AB Growth of a fetus is dependent upon the functional capacity of its placenta, but how the latter is matched to fetal demands is currently unknown. Critically, there is continuous expansion of the feto-placental microvasculature throughout pregnancy, along with morphogenic modifications in the overlying trophoblast epithelium. Here we demonstrate, through fetal and trophoblast specific genetic manipulations in the mouse, that signalling by IGF2 from the feto-placental endothelium and endocrine actions of circulating fetal IGF2 are required. We provide evidence that endothelial and fetal-derived IGF2 plays an important role in trophoblast morphogenesis, acting through Gcm1 and Synb. The effects on placental microvasculature expansion are mediated through IGF2R and angiopoietin-Tie2/TEK signalling. Thus, our study reveals a direct role for IGF2-IGF2R axis on matching fetal demand to placental supply and establishes the principle that hormone-like signals from the fetus play important roles in the control of placental vascularization and trophoblast morphogenesis, findings that have potential clinical implications.