LAUSR

Phosphate transport has been associated with pathological vascular calcification, but this relationship remains largely unexplored in placenta tissue. In this study we investigated the interaction of maternal-fetal phosphate transport and placental calcification using in vitro and in vivo models. Sodium-dependent phosphate transporter transcriptomics validated by quantitative RT-PCR revealed that the type III sodium-dependent phosphate transporter family members Slc20a1 and Slc20a2 are the predominant sodium-dependent symporters in both mouse and human placenta. Global loss of Slc20a2 generates multiple maternal and fetal phenotypes. We examined Slc20a2 promoter activity and protein localization of Slc20a2 throughout placentation. Slc20a2 was detected in embryonic structures that give rise to the maternal-fetal interface and in regions of the placenta that are susceptible to vascular calcification in the absence of Slc20a2. Pathologically, vascular malformations were found to precede calcium deposition in the absence of Slc20a2. Activation of osteocalcin in the placenta suggested that physiological calcification mechanisms may potentiate the mineral deposition observed with Slc20a2 loss. Histological analyses of human placenta revealed focal localization of Slc20a2 protein and distinct calcification deposition patterns. Lastly, the BeWo trophoblast model confirmed cellular competency for active, sodium-dependent phosphate symport as well as extracellular matrix calcification. Taken together, our findings support that normal growth and maintenance of the placenta requires Slc20a2. Moving forward, we now propose the working hypothesis that Slc20a2-mediated placental phosphate transport contributes to the energy requirements for rapid placental vascular development, enabling vascular patterning that maximizes surface area and minimizes tissue damage caused by aberrant flow, thereby promoting organ health and transport of nutrients, including phosphorus, across the placenta.