Naturally occurring perinatal growth restriction in mice programs cardiovascular and endocrine function in a sex- and strain-dependent manner.
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.
Department of Pediatrics, University of Iowa, Iowa, IA 52242, USA. robert-roghair@uiowa.edu
Robert D
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Roghair
Gilbert
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Aldape
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D001835:Body Weight; D002319:Cardiovascular System / Q000196:embryology* / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000196:embryology* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D004703:Endocrine System / Q000196:embryology* / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D005317:Fetal Growth Retardation / Q000378:metabolism / Q000503:physiopathology*; D020022:Genetic Predisposition to Disease; D018149:Glucose Intolerance / Q000196:embryology* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D005951:Glucose Tolerance Test; D006339:Heart Rate; D006973:Hypertension / Q000196:embryology* / Q000503:physiopathology; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D010641:Phenotype; D012720:Severity of Illness Index; D012737:Sex Factors; D013045:Species Specificity
D001786:Blood Glucose; D007328:Insulin