Background: There is a well-established association between maternal gestational diet and fetal development, and the long-term impact on adult disease development. However, there has been little study on the father’s contribution to fetal programming. There is now significant evidence that sub-optimal paternal pre-conception diet can negatively impact the health off offspring in later life. This study examined the impact of a sub-optimal paternal diet on fetal and placental development.
Experimental Design: Male 8-week old C57BL6 mice were fed one of five diets either (i) a control normal protein diet (NPD; 18% casein), (ii) low protein diet (LPD; 9% casein), (iii) high fat diet (HFD; 21.4% fat), (iv) methyl-donor supplemented LPD (MD-LPD) or (v) methyl-donor supplemented HFD (MD-HFD) for 8 weeks. Males were time mated with 8-12 week-old virgin female C57BL6 mice. Fetal and placental weights were measured at embryonic day 17. Placental tissue was collected for morphological and gene expression analysis.
Major Findings: Fetal weight was increased in HFD compared to NPD litters (p=0.031). The addition of methyl-donor supplements prevented the observed fetal-overgrowth. While fetal weight correlated positively to placental weights in NPD and HFD litters (p<0.05), MD-HFD litters demonstrated a negative correlation. Fetal:placental ratios were significantly reduced in MD-HFD litters compared to HFD litters (p=0.049). Placental expression of dimethyl-transferase genes (Dnmt1 and Dnmt3b) were increased in LPD compared to NPD placenta (p<0.05) and decreased in LPD compared to MD-LPD placenta (p<0.01).
Conclusion: This study provides evidence that sub-optimal paternal diet impacts on fetal and placental development. Supplementation with methyl-donors can negate some of these dietary mediated effects, however, further studies are required to ascertain the biological mechanisms and pathways linking paternal diet with the observed changes in fetal growth.