Abstract
Perinatal growth restriction (PGR) is associated with type 2 diabetes and hypertension. Identification of an isogenic mouse model of fetal programming will facilitate mechanistic understanding. We sought to test the hypotheses that 1) PGR impairs glucose tolerance and induces hypertension; and 2) the programming phenotype is more severe in an inbred mouse strain susceptible to diabetes (C57BL/6) than in a strain without such genetic predisposition (DBA/2). PGR pups were paired at weaning with same sex normally grown littermates. Glucose and insulin tolerance tests were performed at 17 wk, and systolic blood pressure (SBP) was measured at 20 wk. Impaired glucose tolerance was evident only among female PGR mice from both strains. While PGR did not alter insulin sensitivity in either strain, female DBA/2 mice had significantly decreased insulin levels during glucose tolerance testing. SBP was increased in PGR male C57BL/6 mice (p < 0.01), while heart rate was decreased in PGR male DBA/2 mice (p < 0.05). These studies indicate that in isogenic mice, PGR alters endocrine and cardiovascular physiology in female and male mice, respectively. Strain-and sex-specific genetic susceptibilities emphasize the need to consider genetic predisposition when evaluating the role of the perinatal environmental in the inception of adult disease.
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Abbreviations
- GTT:
-
glucose tolerance test
- ITT:
-
insulin tolerance test
- PGR:
-
perinatal growth restriction
- SBP:
-
systolic blood pressure
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The authors thank Dr. Curt Sigmund for facilitating use of the tail cuff monitoring apparatus.
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This work was supported by grant K08HD050359 from the National Institutes of Health/National Institute of Child Health & Human Development.
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Roghair, R., Aldape, G. Naturally Occurring Perinatal Growth Restriction in Mice Programs Cardiovascular and Endocrine Function in a Sex- and Strain-Dependent Manner. Pediatr Res 62, 399–404 (2007). https://doi.org/10.1203/PDR.0b013e31813cbf16
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DOI: https://doi.org/10.1203/PDR.0b013e31813cbf16
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