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 diseases 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; which acts as both a barrier and point of exchange between the mother and the developing child. Growth restriction is frequently associated with an oxygen deficient and underdeveloped placenta. Decreased placental oxygenation leads to increased production of harmful molecules which may adversely affect normal development and functioning of the placenta. A stressed placenta also releases abnormal factors into the fetal circulation known to affect development of key fetal organs (e.g. brain, heart). Furthermore, an increase in the release of harmful particles may impact the expression of genetic material in the placenta. Genetic material is not only essential for proper placental function but may also impact fetal organ development. The genetic material is marked by chemical signatures which are easily altered by the womb's environment. The largest producer of harmful molecules is the 'mitochondria' commonly known as 'powerhouse of the cell'. There is now increased interest in assessing the beneficial role of MitoQ - an antioxidant which provides protection against harmful molecules produced in the mitochondria. Previous studies using maternal antioxidants have shown detrimental outcomes in the offspring. 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 a nanoparticle associated delivery is the restriction of the antioxidant to the placental circulation 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 prevent abnormal cardiac development and disease in later life.