The AKT1-FOXO4 axis reciprocally regulates hemochorial placentation.
Development
; 150(2)2023 01 15.
Article
en En
| MEDLINE
| ID: mdl-36607602
ABSTRACT
Hemochorial placentation involves the differentiation of invasive trophoblast cells, specialized cells that possess the capacity to exit the placenta and invade into the uterus where they restructure the vasculature. Invasive trophoblast cells arise from a well-defined compartment within the placenta, referred to as the junctional zone in rat and the extravillous trophoblast cell column in human. In this study, we investigated roles for AKT1, a serine/threonine kinase, in placental development using a genome-edited/loss-of-function rat model. Disruption of AKT1 resulted in placental, fetal and postnatal growth restriction. Forkhead box O4 (Foxo4), which encodes a transcription factor and known AKT substrate, was abundantly expressed in the junctional zone and in invasive trophoblast cells of the rat placentation site. Foxo4 gene disruption using genome editing resulted in placentomegaly, including an enlarged junctional zone. AKT1 and FOXO4 regulate the expression of many of the same transcripts expressed by trophoblast cells, but in opposite directions. In summary, we have identified AKT1 and FOXO4 as part of a regulatory network that reciprocally controls critical indices of hemochorial placenta development.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Placenta
/
Placentación
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Pregnancy
Idioma:
En
Revista:
Development
Asunto de la revista:
BIOLOGIA
/
EMBRIOLOGIA
Año:
2023
Tipo del documento:
Article
País de afiliación:
Estados Unidos