Decipher the function of TRPV2 in trophoblast giant cells.

Intrauterine growth restriction (IUGR) refers to the failure of the fetus to achieve its genetically determined growth potential and affects up to 5-10% of pregnancies. Growth restricted neonates have increased perinatal mortality rates and are more susceptible to develop adult metabolic diseases. Our unpublished results showed that mice lacking TRPV2 display late-onset IUGR caused by placental weight deceleration at E15.5, followed by fetal growth restriction at E16.5. Additionally, TRPV2 mRNA was robustly found in trophoblast giant cells (TGC). Here, we aim to investigate the function of TRPV2 in TGC during placental development. First, we aim to assess the spatiotemporal expression pattern of TRPV2 in TGC and its role in functions such as invasion and phagocytosis. Next, the placental phenotype will be investigated at morphological and functional level. Additionally, the growth restricted offspring will be monitored to assess their susceptibility to develop diabetes and hypertension. To do so, a conditional knockout will be used that lacks TRPV2 in Tpbpa-positive TGC, since TRPV2 is broadly expressed in the adult mice. Finally, TRPV2 expression will be assessed in human placentas of normal and IUGR pregnancies. In addition, DNA will be analyzed to discover possible polymorphisms in TRPV2 that could be the cause for IUGR. The results of this project hold great clinical potential to identify new causative factors for IUGR that might be used for prenatal screening.