Funding outcome

Birth with a congenital heart defect (CHD) causes more infant deaths than birth with any other birth defects. The cause of at least 50% of CHDs is unknown. Recently, it has been suggested that placental function may impact heart development, and placental pathology is common in more severe CHD. Whether placental dysfunction causes some of the unexplained CHD remains unknown. Placental malfunction can impair the general health of the fetus. In identical twins who share one placenta, umbilical blood from one twin (donor) courses through the other twin's (recipient) placenta causing release of blood vessel constrictors (e.g. Endothelin, ET-1) from the placenta into the recipient ciculation. This condition, known as twin-twin transfusion syndrome (TITS), is associated with 20% of the death and poor outcomes of all twin pregnancies. The reasons for TITS are not well understood but the recipient baby is at particularly high risk of heart dysfunction and structural CHD. We suspect altered placenta production of blood vessel constrictors may contribute to the development of heart dysfunction and CHD in the recipient twin and provides unique insight into the placental-(fetal) heart axis. There have been no animal models used to explore the placenta's relationship to heart development in detail. In this study, we will investigate the link between the placenta and fetal heart form and function through a novel approach. Using a mouse model, a gene of a blood vessel constrictor (ET-1) will be introduced into the placenta with an 'on' switch to increase production above normal amounts at various fetal stages. Fetal heart formation and function, and signs of abnormal placental function and blood flow will be assessed.