Funding outcome

It is now recognized that an inadequate environment within a mother's womb can adversely affect the fetus and increase the risk of cardiovascular disease in adult life. A fetus that does not get enough supply of oxygen and nutrients maybe born growth restricted. The organ responsible for supplying the developing fetus with adequate resources is the placenta. The placenta acts both as a barrier and point of nutrient and waste exchange between the mother and the developing child. Growth restriction is frequently associated with an oxygen deficient and underdeveloped placenta. Decreased placental oxygen availability leads to increased production of harmful molecules (oxidants) that may adversely affect normal development and functioning of the placenta. Such oxidants become more abundant in the placenta when the availability of helpful molecules (antioxidants) decreases. Oxidants can reduce the supply of oxygen to the fetus by breaking down substances that promote normal placental function and additionally, produce toxic compunds detrimental to placental development. The largest producer of oxidants is the 'mitochondria' inside the cell. There is now increased interest in assessing the beneficial role of the antioxidant, MitoQ which provides protection against oxidants produced by the mitochondria. However, previous studies giving antioxidants to the mother have shown adverse effects on the fetus. Therefore, in our current study we will investigate treatment of an animal model of growth restriction with MitoQ attached to nanoparticles (nMitoQ). The advantage of using the nanoparticles is the restriction of the antioxidant to the mother and placenta without crossing the placental barrier and allowing access to the fetal circulation; thereby avoiding off target effects on the fetus. We hypothesize that treatment with nMitoQ will restore placental function and will thereby prevent abnormal cardiac development and disease in later life.