Objectives: Deletion of the placental-specific P0 transcript of the insulin-like growth factor gene (Igf2) reduces placental growth from early pregnancy onwards. In Igf2 P0 knockout fetuses (P0), maternofetal flux of (14)C-methylaminoisobutyric acid ((14)C-MeAIB) mediated by system A amino acid transporter activity is increased at embryonic day 16 (E16), but this stimulation is not sustained, and by E19, fetal growth restriction (FGR) ensues. Here, we investigated whether upregulated (14)C-MeAIB transfer does occur concomitantly with a change in System A amino acid transporter activity and whether altered uteroplacental vascular function contributes to the FGR. We tested the hypothesis that FGR in P0 mice is attributable to altered nutrient transport rather than aberrant uteroplacental vascular function.
Methods: Plasma membrane vesicles were isolated from placentas of P0 and wild-type (WT) fetuses at E16 and E19. System A amino acid transporter activity was measured as sodium-dependent (14)C-MeAIB uptake over 60s. Wire myography was performed on uterine artery branches supplying P0 or WT implantation sites and agonist-induced constriction and dilation measured.
Results: Sodium-dependent uptake of (14)C-MeAIB (at 60s) was significantly (P < 0.05) higher in P0 compared to WT vesicles at E16; at E19 (14)C-MeAIB uptake was similar between P0 and WT. Uterine artery branch vascular reactivity was comparable between groups.
Conclusions: System A activity in the maternal-facing plasma membrane of syncytiotrophoblast layer II underpins the adaptations observed in the transplacental MeAIB flux of P0 mice. Unaltered uterine artery vascular function suggests that the FGR phenotype of P0 fetuses is primarily due to deficient placental nutrient exchange capacity.
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