Raised Late Pregnancy Glucose Concentrations in Mice Carrying Pups With Targeted Disruption of H19(Δ13)

OBJECTIVE: We have hypothesized that variation in imprinted growth-promoting fetal genes may affect maternal glucose concentrations in pregnancy. To test this hypothesis we evaluated the effects of fetal disruption of murine H19(Δ13) on maternal glucose concentrations in pregnancy. RESEARCH DESIGN AND METHODS: Experimental mice were pregnant females that had inherited the disrupted H19(Δ13) from their fathers and were therefore phenotypically wild type due to imprinting; approximately half of their litters were null for H19(Δ13) through maternal inheritance of the disrupted gene. In control mice approximately half the litter paternally inherited the disrupted H19(Δ13), so the pups were either genetically wild type or phenotypically wild type due to imprinting. Blood glucose concentrations were assessed by intraperitoneal glucose tolerance tests on days 1, 16, and 18 of pregnancy. RESULTS: There were no differences in the glucose concentrations of control and experimental pregnant mice at day 1. However, at day 16 mothers carrying H19(Δ13)-null pups had a significantly higher area under the glucose tolerance test curves than controls (1,845 ± 378 vs. 1,386 ± 107 mmol · min · l(−1) [P = 0.01]) in association with increasing pregnancy-related insulin resistance. Although this difference lessened toward term, overall, mothers of maternally inherited H19(Δ13) mutants had significantly higher glucose concentrations during the last trimester (1,602 ± 321 [n = 17] vs. 1,359 ± 147 [n = 18] mmol · min · l(−1) [P = 0.009]). CONCLUSIONS: This study provides evidence that maternal glucose concentrations in pregnant mice can be affected by targeted disruption of fetal H19(Δ13). This implies that variable fetal IGF2 expression could affect risk for gestational diabetes.