System A activity and vascular function in the placental-specific Igf2 knockout mouse

L. C. Kusinski, M. R. Dilworth, P. N. Baker, C. P. Sibley, M. Wareing, J. D. Glazier

    Research output: Contribution to journalArticlepeer-review


    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 14C-methylaminoisobutyric acid ( 14C-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 14C-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 14C-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 14C-MeAIB (at 60s) was significantly (P <0.05) higher in P0 compared to WT vesicles at E16; at E19 14C-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. © 2011 Elsevier Ltd. All rights reserved.
    Original languageEnglish
    Pages (from-to)871-876
    Number of pages5
    Issue number11
    Publication statusPublished - Nov 2011


    • Amino acid
    • Fetal growth restriction
    • Growth factors
    • Nutrient transport
    • Uterine artery


    Dive into the research topics of 'System A activity and vascular function in the placental-specific Igf2 knockout mouse'. Together they form a unique fingerprint.

    Cite this