Abstract P228: RhoBTB1 Is Expressed In Placental Syncytiotrophoblast Cells

Abstract

Preeclampsia is a pregnancy-specific disorder of hypertension and end-organ dysfunction that poses serious clinical problems for women and their offspring that extend beyond the peripartum period. Abnormal placentation is at the core of preeclampsia. PPARγ-deficient mice exhibit numerous placental defects including malformation of the labyrinth zone, lack of infiltration of fetal blood vessels, and rupture of maternal blood sinuses, suggesting that PPARγ is a critical regulator of placental development and possibly function. Rho-related BTB domain-containing protein 1 (RhoBTB1) is a PPARγ target gene which controls the level of cGMP in vascular smooth muscle cells by functioning as an adaptor delivering phosphodiesterase 5 (PDE5) to the Cullin-3 ubiquitin ligase complex. Analysis of gene expression databases revealed that placenta is among the tissues with the highest level of RhoBTB1 expression. Thus, we examined if the level or cell-specificity of RhoBTB1 expression was altered in preeclampsia. Placental samples were obtained from the Medical College of Wisconsin Maternal Research Placenta and Cord Blood Bank. We examined placentas from term healthy (n=3), preterm non-preeclamptic (n=2), term preeclamptic (n=2) and preterm preeclamptic (n=2) pregnancies. RNAscope in situ hybridization was used to qualitatively evaluate expression of RhoBTB1 and several placental markers. Our results reveal that RhoBTB1 co-localizes with CYP19A1, a gene encoding cytochrome P450 enzyme, a target specific to the syncytiotrophoblast cell layer in the placenta. Expression of RhoBTB1 was not co-localized with platelet-endothelial cell adhesion molecule-1 (PECAM) or with melanoma cell adhesion molecule (MCAM), both endothelial cell markers. These results indicate that RhoBTB1 is specifically expressed in the syncytiotrophoblast cell layer in human placentas. This finding persisted in preterm and preeclamptic placental samples. These data compel us to assess the functional significance of placental RhoBTB1 using conditional knockout and a conditional activatable RhoBTB1 models. Further investigative work is being done to determine if placental RhoBTB1 expression is altered based on ethnic and racial differences.