With increasing obesity and diabetes in our population, and alcohol,
marijuana, and tobacco use among women of child-bearing years, there is a high
probability of embryonic exposure to risk factors before pregnancy is recognized.
These metabolic changes and environmental factors are known in animals to induce
birth defects and specifically, congenital heart defects (CHDs). This study discusses an
interrelationship between placental and heart development in which blood flow
between these developing organs needs to be maintained at specific levels. When blood
flow is altered in the mouse by embryonic exposure to environmental factors,
dysmorphogenesis occurs. Additionally, with gene expression analysis of the
embryonic heart it was demonstrated that with elevated homocysteine (HCy) a natural
metabolite, and alcohol exposures, numerous Gene Ontology classifications relating to
lipid metabolism were altered. As for example, relative to the female embryo,
significantly more alterations occurred in the male embryonic heart transcriptome with
homocysteine exposure. That lipid metabolism was altered was validated by staining
for localization of neutral lipids in the embryonic mouse embryos. We demonstrated
that lipid droplet amount and the localization patterning were changed with exposures
in both the fetal four-chambered heart and in the placenta. More changes occurred,
however, in the placental tissue. We have demonstrated that a regimen of high folic
acid supplementation of the pregnant mouse diet started with the morning after
conception prevented the environmentally induced alterations. The importance of lipids
in trophoblast and placental development, the relationship to gender, and how folate
supplementation normalizes development through epigenetic programming is
reviewed.
Keywords: Alcohol, Bioinformatics, Congenital heart defects, Environmental effects, Ethanol, Gender, Heart, Homocysteine, Human embryology, Lithium, Lipid metabolism, Mouse embryo, Placenta, Trophoblasts.
