Phosphoinositide 3-Kinase (PI3K) Subunit p110? Is Essential for Trophoblast Cell Differentiation and Placental Development in Mouse.
ABSTRACT: Maternal PI3K p110? has been implicated in smaller litter sizes in mice, but its underlying mechanism remains unclear. The placenta is an indispensable chimeric organ that supports mammalian embryonic development. Using a mouse model of genetic inactivation of PI3K p110? (p110?(D910A/D910A)), we show that fetuses carried by p110?(D910A/D910A) females were growth retarded and showed increased mortality in utero mainly during placentation. The placentas in p110?(D910A/D910A) females were anomalously anemic, exhibited thinner spongiotrophoblast layer and looser labyrinth zone, which indicate defective placental vasculogenesis. In addition, p110? was detected in primary trophoblast giant cells (P-TGC) at early placentation. Maternal PI3K p110? inactivation affected normal TGCs generation and expansion, impeded the branching of chorioallantoic placenta but enhanced the expression of matrix metalloproteinases (MMP-2, MMP-12). Poor vasculature support for the developing fetoplacental unit resulted in fetal death or gross growth retardation. These data, taken together, provide the first in vivo evidence that p110? may play an important role in placental vascularization through manipulating trophoblast giant cell.
PROVIDER: S-EPMC4910077 | BioStudies | 2016-01-01T00:00:00Z