The Potential Role of Trophoblast Slc20a2 Mutations in Vascular Calcification of the Placenta

Overview

Tufts Medical Center Any dysfunction of the placenta can negatively impact maternal-fetal health and cause placental insufficiency, which can lead to issues such as stillbirth and congenital heart defects. One particularly harmful complication is vascular calcification. Sodium-dependent phosphate transporter 2 (PiT-2), which is encoded by the Slc20a2 gene, lead to novel therapeutic treatments for vascular calcification. To determine the cell type that expresses Slc20a2 and to discern the location of calcification in the placenta, fluorescence in situ hybridization (FISH), Alizarin Red staining, and immunofluorescence staining were performed on wild-type and Slc20a2 knockout mouse placental tissues. Alizarin Red staining showed that Slc20a2 knockout mice had significantly greater areas of calcification than wildtype mice. The calcium deposits were located within the intracellular space and extracellular matrix of the chorionic plate and labyrinth regions of the mouse placenta. Similarly, immunofluorescence staining combined with FISH revealed that Slc20a2 mRNA was found in the trophoblasts of vascular spaces within the chorionic plate and labyrinth. This indicates anatomical co-localization of regions of calcification and Slc20a2 mRNA expression in the placenta. The findings suggest that deleterious mutations of the Slc20a2 gene may result in vascular calcification of the placenta. Furthermore, Slc20a2 gene expression in the trophoblasts of the labyrinth and chorionic plate may play a major role in preventing or mitigating placental vascular calcification.