Altered metabolism of maternal micronutrients and omega 3 fatty acids epigenetically regulate matrix metalloproteinases in preterm pregnancy: a novel hypothesis.

Preterm birth is an important perinatal health problem. Several possible mechanisms have been proposed but it may be important to have a testable mechanistic hypothesis that can explain the possible common mechanism for preterm births around the globe. Altered metabolism of micronutrients, like folic acid, vitamin B(12), zinc and copper are known to be associated with adverse pregnancy outcomes such as preterm birth. We have recently reported that increased oxidative stress and reduced docosahexaenoic acid levels are associated with preterm delivery. Matrix metalloproteinases and their tissue inhibitors play vital roles in extracellular matrix remodelling/degradation during pregnancy. Expression and the activity of matrix metalloproteinases have been shown to be regulated by oxidative stress and hyperhomocysteinemia. We have recently reported gestation dependant changes in placental global methylation levels. Here, we propose a novel hypothesis that altered maternal micronutrients (folic acid, vitamin B(12)), omega 3 fatty acids, and consequent oxidative stress lead to altered epigenetic mechanisms resulting in altered expression of matrix metalloproteinases and their tissue inhibitors during pregnancy. This may have important implications in the epigenetic programming of adult diseases since preterm infants are known to be at increased risk for neurodevelopmental, metabolic and cardiovascular dysfunctions in later life.