Both complete knockout of the Igf2 gene (Igf2null(+/-)) and knockout of its placental specific transcript alone (Igf2P0(+/-)) lead to fetal growth restriction in mice. However, in the Igf2null(+/-) this growth restriction occurs concurrently in gestation with placental growth restriction, whereas, placental growth restriction precedes fetal growth restriction in the Igf2P0(+/-) mouse. Previous studies have shown that the Igf2P0(+/-) placenta has proportionate reductions in its cellular compartments and its diffusional exchange characteristics. Yet, nothing is known about the structural development or diffusional exchange characteristics of the Igf2null(+/-) mouse. Hence, this study compares the structural properties (using stereology) and diffusional exchange characteristics (using measurement of permeability-surface area product, P.S, of three inert hydrophilic tracers) of the Igf2null(+/-) and the Igf2P0(+/-) placenta to identify the role of Igf2 in the development of the labyrinthine exchange membrane and its functional consequences. Our data show disproportionate effects of complete Igf2 ablation on the compartments of the placenta, not seen when the placental-specific transcript alone is deleted. Furthermore, although the theoretical diffusing capacity (calculated from the stereological data) of the Igf2null(+/-) placenta was reduced relative to control, there was no effect of the complete knockout on permeability surface area available for small hydrophilic tracers. This is in contrast to the Igf2P0(+/-) placenta, where theoretical diffusion capacity and P.S values were reduced similarly. Total ablation of the Igf2 gene from the fetoplacental unit in the mouse therefore results in a disproportionate growth of placental compartments whereas, deleting the placental specific transcript of Igf2 alone results in proportional placental growth restriction. Thus, placental phenotype depends on the degree of Igf2 gene ablation and the interplay between placental and fetal Igf2 in the mouse.
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