The placenta functions as a conduit between the mother and the developing fetus and is essential for fetal growth. Unfortunately, a large proportion of pregnancies are affected by complications arising from inadequate placentation. Requisite to understanding these pathologies is first understanding healthy placental development. In this vein, we aimed to determine the role of the Dynamin isoforms (DNM 1, 2 & 3), a superfamily of mechanoenzymes classically involved in endocytotic and exocytotic processes, in the placenta.
Q-PCR and western blotting approaches were used to confirm the expression of DNM at the mRNA and protein level in both first trimester and term human placentae, while complimentary immunocytochemical and immunohistochemical analyses provided crucial information relative to the localization of DNM. These analyses revealed that all 3 DNM isoforms were expressed at the mRNA level, however only DNM2 and DNM3 were expressed at the protein level. DNM2 protein expression was significantly more abundant in term placentae (P<0.0001) compared to first trimester placentae. DNM2 was uniformly distributed in the syncytiotrophoblast, with enrichment toward the apical margin. Whereas DNM3 was distributed throughout the cytosol of both cytotrophoblast and syncytiotrophoblast cells. In addition, western blotting indicated that DNM2 and 3 were significantly downregulated in placentae from women with preeclampsia (P<0.05).
In an effort to understand the functional role of placental DNM, the BeWo choriocarcinoma cell line was cultured with the dynamin inhibitor ‘Dynasore’. Dynamin inhibition results in an overall reduction in the secretome of BeWo cells. Furthermore, analysis of the individual bands detected by silver stain demonstrated that the secretion of a protein at ~29kDa was significantly reduced (P<0.01), putatively corresponding to the soluble (pro)renin receptor (s(P)RR)). Since women with preeclampsia are known to exhibit increased maternal levels of s(P)RR, future analyses will focus on unraveling the contribution of DNM to the pathogenesis of preeclampsia.