Abstract:
The placenta is a fetal organ that nourishes the unborn baby within its mother’s womb and supports it through the most critical developmental phase of its life. However, in spite of the cardinal role the placenta plays in ensuring fetal health, our understanding of normal, and abnormal, placental development is nebulous, with the determinants of placental development not yet fully defined. This thesis investigates whether shear stress exerted upon the placental surface; the syncytiotrophoblast, as a result of fluidic flow around the placenta is one such determinant that regulates placentogenesis. This thesis reports the in-vivo expression of mechanosensitive proteins; Dynein-2, IFT88, Kinesin-2, Piezo1, Polycystin-2 and TRPV6 in the syncytiotrophoblast of fresh frozen tissue derived from first trimester (n=3), normal term (n=3) and pathological FGR (n-3) placentae. A corresponding in-vitro expression of Dynein-2, IFT88, Kinesin-2, Polycystin-2 and TRPV6 is reported in a first trimester culture of syncytiotrophoblasts. Additionally, first trimester (n=5) and term (n=5) tissue is imaged in 3D via micro-computerized tomography, to enable quantitative blood flow simulations that can predict the shear stress exerted upon the syncytiotrophoblast across gestation. Together, this thesis provides novel evidences that the syncytiotrophoblast, across gestation, and in pathological cases, is capable of mechanosensation. Furthermore, it validates and enables future experiments that can directly assess the response of the syncytiotrophoblast to physiological shear stresses predicted by mathematical models.