期刊
DEVELOPMENTAL CELL
卷 57, 期 1, 页码 63-+出版社
CELL PRESS
DOI: 10.1016/j.devcel.2021.12.005
关键词
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资金
- Biotechnology and Biological Sciences Research Council [BB/H003312/1]
- Medical Research Council [MRC_MC_UU_12012/4, MRC_MC_UU_12012/5, MR/R022690/1]
- Spanish Ministry of Science and Innovation [RYC-2019-026956, PID2020-114459RA-I00]
- Wellcome Trust (Sir Henry Wellcome Postdoctoral Fellowship) [220456/Z/20/Z]
- Royal Society (Dorothy Hodgkin Research Fellowship) [DH130036]
- Centre for Trophoblast Research
- NIHR Cambridge BRC Cell Phenotyping Hub
- Wellcome Trust [220456/Z/20/Z] Funding Source: Wellcome Trust
- Royal Society [DH130036] Funding Source: Royal Society
This study demonstrates the vital role of endothelial and fetus-derived IGF2 in the expansion of the feto-placental microvasculature and trophoblast morphogenesis. It reveals that fetal signals play an important role in controlling placental development and highlights the significance of the imprinted Igf2-Igf2r axis in matching placental development to fetal growth.
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.
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