Developmental adaptations to increased fetal nutrient demand in mouse genetic models of Igf2-mediated overgrowth

被引:49
作者
Angiolini, Emily [1 ,3 ,4 ]
Coan, Phillip M. [2 ]
Sandovici, Ionel [1 ,2 ,4 ]
Iwajomo, O. H. [3 ]
Peck, Gerrard [1 ,4 ]
Burton, Graham J. [2 ]
Sibley, Colin P. [5 ]
Reik, Wolf [2 ,3 ]
Fowden, Abigail L. [2 ]
Constancia, Miguel [1 ,2 ,4 ]
机构
[1] Univ Cambridge, Dept Obstet & Gynaecol, Metab Res Labs, Cambridge CB2 0SW, England
[2] Univ Cambridge, Dept Physiol Dev & Neurosci, Ctr Trophoblast Res, Cambridge CB2 0SW, England
[3] Babraham Inst, Lab Dev Genet & Imprinting, Cambridge, England
[4] Cambridge Biomed Res Ctr, Natl Inst Hlth Res, Cambridge, England
[5] Univ Manchester, St Marys Hosp, Manchester Acad Hlth Sci Ctr, Maternal & Fetal Hlth Res Ctr,Sch Biomed, Manchester M13 0JH, Lancs, England
基金
英国医学研究理事会; 英国生物技术与生命科学研究理事会;
关键词
genomic imprinting; insulin-like growth factor; H19; placenta; BECKWITH-WIEDEMANN; PLACENTAL EFFICIENCY; IGF-II; TRANSPORT; INSULIN; GROWTH; DELETION; OBESITY; REGION; MICE;
D O I
10.1096/fj.10-175273
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The healthy development of the fetus depends on an optimal balance between fetal genetic drive for growth and the maternal ability to provide nutrients through the placenta. Nothing is known about fetal-placental signaling in response to increased fetal demand in the situation of overgrowth. Here, we examined this question using the H19(Delta 13) mouse model, shown previously to result in elevated levels of Igf2. Fetal and placental weights in H19(Delta 13) were increased by 23% and 45%, respectively, at E19, when compared with wild-type mice. Unexpectedly, we found that disproportionately large H19(Delta 13) placentas transport 20-35% less (per gram placenta) glucose and system A amino acids and have similar reductions in passive permeability, despite a significantly greater surface area for nutrient exchange and theoretical diffusion capacity compared with wild-type mice. Expression of key transporter genes Slc2a3 and Slc38a4 was reduced by similar to 20%. Decreasing the overgrowth of the H19(Delta 13) placenta by genetically reducing levels of Igf2P0 resulted in up-regulation of system A activity and maintenance of fetal overgrowth. Our results provide direct evidence that large placentas can modify their nutrient transfer capacity to regulate fetal nutrient acquisition. Our findings are indicative of fetal-placental signaling mechanisms that limit total demand for maternal nutrients.-Angiolini, E., Coan, P.M., Sandovici, I., Iwajomo, O.H., Peck, G., Burton, G.J., Sibley, C.P., Reik, W., Fowden, A.L., Constancia, M. Developmental adaptations to increased fetal nutrient demand in mouse genetic models of Igf2-mediated overgrowth. FASEB J. 25, 1737-1745 (2011). www.fasebj.org
引用
收藏
页码:1737 / 1745
页数:9
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