The imprinted Igf2-Igf2r axis is critical for matching placental microvasculature expansion to fetal growth.
Dev Cell
; 57(1): 63-79.e8, 2022 01 10.
Article
em En
| MEDLINE
| ID: mdl-34963058
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Placenta
/
Fator de Crescimento Insulin-Like II
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Receptor IGF Tipo 2
Limite:
Animals
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Pregnancy
Idioma:
En
Revista:
Dev Cell
Assunto da revista:
EMBRIOLOGIA
Ano de publicação:
2022
Tipo de documento:
Article