180: Do genetic and environmental influences on abnormal metabolic profile in pregnancy continue to second generation offspring?


      Fetal programming contributes to metabolic and cardiovascular disease in offspring even during their adult life. Whether fetal programming increases the risks for disease in subsequent generations remain unknown. Our aim was to evaluate the effect of genetic and environmental inheritance on the metabolic profile in a transgenerational mouse model.

      Study Design

      In order to study the effects of fetal programming on 2nd generation offspring we conducted three breeding schemes, all with wild type (WT) males. WT males were bred to heterozygous eNOS+/- females fed a high fat diet (HFD) manifesting metabolic-like syndrome (MLS) phenotype (Group 1), heterozygous eNOS+/- females fed a control diet (CD) manifesting hypertension (HTN) (Group 2), or WT female fed CD use as control (Group 3). WT male offspring from these groups (2nd generational animals) were then fed control diet from weaning to until 3 months of age after weaning. Offspring weight was measured from 3 weeks to 8 weeks of age to obtain weight gain trajectory. Systolic blood pressure (SBP), glucose tolerance test (GTT) and lipid profile (cholesterol, HDL, LDL and triglycerides) were measured at 3 months of age.


      WT offspring born from MLS mother had similar postnatal weight gain at 8 weeks of age (MLS, group 1: 8.8 ± 0.7 g) compared with offspring born from HTN and control mother (HTN, group 2: 12.3 ± 2.3 g; control, group 3: 11.3 ± 0.5 g)(p=0.172). Among the three groups, similar glucose levels were obtained by GTT at each time-point of the curve. There was no difference in SBP among all the WT male offspring groups (MLS, group 1: 156.9 ± 5.5; HTN, group 2: 134.2 ± 11.9 and control, group 3: 138.9 ± 6.3, p=0.137). Also no difference was seen in the lipid profile between groups (Table, p=0.994 for cholesterol; p=0.984 for HDL; p=0.980 for LDL; p=0.998 for TG).


      This is one of the first studies to evaluate the effects of fetal programming on 2nd generation offspring. Abnormal metabolic profiles resulting from genetic and environmental exposures in first generation female during pregnancy do not appear to increase the risk of passage of metabolic or cardiovascular dysfunction to the 2nd generation animals fed a normal diet.
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