Expression of agouti-related peptide, neuropeptide Y, pro-opiomelanocortin and the leptin receptor isoforms in fetal mouse brain from pregnant dams on a protein-restricted diet

Expression of agouti-related peptide, neuropeptide Y, pro-opiomelanocortin and leptin receptor isoforms were found in fetal mouse brain at embryonic day 12 (E12). Levels of expression for these genes were altered in brains of E12 fetuses from pregnant dams on a protein-restricted diet, suggesting that the fetal brain is responsive to changes in maternal nutrition prior to birth

Elevated BNP expression in mouse offspring left ventricles after protein restriction in utero

Objectives: We have previously shown that cyclin G1expression is reduced in fetal hearts after in utero protein restriction (PR) suggesting reduced cardiac cell cycle. However no difference in cyclin G1 expression was seen in adult offspring hearts. We hypothesised that the hearts of adult PR group should be under greater stress to maintain cardiac output. We therefore measured brain natriuretic peptide (BNP) expression in fetal hearts and left ventricles of adult offspring in the control (C) and PR groups because BNP is a marker of left ventricular dysfunction during volume overload or cardiac fibrosis (Nishikimi et al. Cardiovasc Res. 2006).Methods and results: Pregnant CD1 mice were placed on C (18% casein) or PR (9% casein) diet. Fetal hearts were collected on day 12 of gestation (C, n =11, PR, n =10) and the left ventricles (LV) of adult offspring at 6 months (C,n =17, PR, n =17). Fetal heart BNP mRNA expression relative to unit total RNA as measured by real-time PCR was similar in C and PR (C, 0.858F0.104 vs. PR, 0.761F0.096, p =NS). However, BNP expression in adult LV was greater in the PR than C (C, 7.043F0.68 vs. PR, 11.012F1.54, p =0.04).Conclusion: These results indicate that protein restriction in pregnancy induces cellular changes (indicated by cyclin G1 changes) in the fetal heart which places it under stress in adulthood (elevated BNP production). Because BNP can suppress ventricular remodelling, we are presently investigating cardiac structural changes to assess whether these alterations are adaptive or maladaptive

Impact on the developmental profile of the murine heart by maternal protein restriction during preganancy

Aims: We hypothesised that intrauterine environmental factors such as undernutrition may have an impact on cardiac development in prenatal life, leading to cardiac hypertrophy. In this study, we examined the effects of maternal dietary protein restriction (PR) during pregnancy on fetal heart development in the mouse. Study design and Subjects: CD1 mice were placed on control C (18% casein) or protein restricted PR (9% casein) diet during pregnancy. Fetal hearts were collected on day 12 of gestation and the left ventricles (LV) of adult offspring at 6 months.Outcome Measures: p53, e2f1 mRNA expression was measured by real time RT PCR, fetal heart ventricular volumes and surface area of by MRI.Results: No differences were demonstrated in p53 and E2f1 expression in fetal heart or adult LV. MRI revealed smaller hearts in the PR group, both for surface area (PR, 13831±68 vs. C, 16356±37 mm2, p<0.01) and ventricular volume (PR, 22114±43 v C, 27404±10 mm3; p<0.001).Conclusion: These results indicate that protein restriction during pregnancy leads to a smaller fetal heart (MRI scan), perhaps due to its effect on cell allocation and division. Lack of difference in the expression of p53 and E2f1, genes involved in cell inhibition and apoptosis and cell proliferation, respectively in either group suggest that changes in fetal heart size are due to the reduction of cardiomyocyte growth (supported by lower cyclin g1 expression previously described) in the PR group