You are what you eat, and so are your children: the impact of micronutrients on the epigenetic programming of offspring

Abstract

The research field of fetal programming has developed tremendously over the years and increasing knowledge suggests that both maternal and paternal unbalanced diet can have long-lasting effects on the health of offspring. Studies implicate that macronutrients play an important role in fetal programming, although the importance of micronutrients is also becoming increasingly apparent. Folic acid and vitamins B2, B6 and B12 are essential for one-carbon metabolism and are involved in DNA methylation. They can therefore influence the programming of the offspring's epigenome. Also, other micronutrients such as vitamins A and C, iron, chromium, zinc and flavonoids play a role in fetal programming. Since it is estimated that approximately 78 % of pregnant women in the US take vitamin supplements during pregnancy, more attention should be given to the long-term effects of these supplements on offspring. In this review we address several different studies which illustrate that an unbalanced diet prior and during pregnancy, regarding the intake of micronutrients of both mother and father, can have long-lasting effects on the health of adult offspring.

Fig. 1

Transgenerational inheritance of epigenetic modifications induced by exposure to macro- and micronutrients

Fig. 2

Hypothetical concept regarding the difference in fetal programming induced by genistein obtained from a Western or Asian diet. In the case of an Asian diet, genistein is taken up by the mother, via dietary sources prior to, during and after pregnancy, while the offspring remains exposed to dietary genistein throughout its life, resulting in a decreased risk for breast and prostate cancer. In the case of a Western diet, genistein levels are low, although they can be increased due to supplement intake. The fetus adapts to these low levels of genistein; however, once born these levels may not be attained via the diet, potentially affecting the risk for offspring to develop breast or prostate cancer later in life

Fig. 3

Simplified schematic of the folic acid metabolic pathway resulting in DNA methylation. Methylation of DNA occurs via the folic acid metabolic pathway. In this pathway the micronutrient folic acid (vitamin B9) is first reduced to dihydrofolate (DHF), which is then reduced to tetrahydrofolate (THF). 5,10-methylene-THF (5,10-MTHF) is formed by adding a methylene group to THF. In this step of the pathway, vitamin B6 (B6) serves as an essential co-enzyme. Next, 5,10-MTHF is reduced to 5-methyl THF (5-MTHF) with the aid of the essential co-enzyme vitamin B2 (B2). 5-MTHF then donates, with the co-enzyme, vitamin B12 (B12), its methyl group to homocysteine, resulting in the formation of methionine. Subsequently, methionine donates its methyl group to DNA via S-adenosyl-methionine (SAM). SAH s-adenosylhomocysteine

Fig. 4

Hypothetical health consequences of prenatal diets upon trigger at adulthood. Whether or not the prenatal diet will have a pre-emptive effect and be beneficial at adult age, or whether it will have deleterious effects later in life may depend upon the composition of the diet, the fetal adaptations and subsequent disease triggers later in life. For instance, in the case of diet 1, an increase in antioxidant intake by the mother during pregnancy decreased the ROS levels in the fetus, to which it adapts. If during the offspring’s adult life, its antioxidant defense system is triggered, excessive oxidative stress can occur because the offspring did not ‘learn’ in utero how to cope with these increased levels of ROS. In the case of diet 2, the maternal diet during pregnancy consisted of lower levels of antioxidants or increased triggers of the Nrf2 pathway. Again, the fetus will adapt to these conditions, and in adulthood, when the antioxidant defense system of this offspring is triggered, this can result in an improved response since the offspring adapted and ‘learned’ in utero how to cope with such a trigger