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Disproportional effects of Igf2 knockout on placental morphology and diffusional exchange characteristics in the mouse
Author(s) -
Coan P. M.,
Fowden A. L.,
Constancia M.,
FergusonSmith A. C.,
Burton G. J.,
Sibley C. P.
Publication year - 2008
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2008.157313
Subject(s) - placenta , biology , stereology , null allele , fetus , knockout mouse , conditional gene knockout , fetal growth , intrauterine growth restriction , microbiology and biotechnology , andrology , endocrinology , medicine , chemistry , gene , phenotype , genetics , pregnancy
Both complete knockout of the Igf2 gene ( Igf2 null +/− ) and knockout of its placental specific transcript alone ( Igf2 P0 +/− ) lead to fetal growth restriction in mice. However, in the Igf2 null +/− this growth restriction occurs concurrently in gestation with placental growth restriction, whereas, placental growth restriction precedes fetal growth restriction in the Igf2 P0 +/− mouse. Previous studies have shown that the Igf2 P0 +/− 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 Igf2 null +/− 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 Igf2 null +/− and the Igf2 P0 +/− 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 Igf2 null +/− 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 Igf2 P0 +/− 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.