Phosphate transporter roles in mammalian placenta.

The placenta, a poorly understood organ, is required for support of embryonic development and maintenance of maternal health. Placental dysfunction can lead to preeclampsia, uterine growth restriction, stillborn births, and maternal death. Low placental expression of the phosphate transporter Slc20a2 has been correlated with preeclampsia, a cardiovascular pregnancy-specific syndrome thought to be caused placental vascular dysfunction. In this study we sought to test the specific hypothesis that loss of Slc20a2 is required for normal placental function and support of embryonic development. To test this hypothesis, we first characterized a novel Slc20a2 deficient mouse model. Embryonic development was assessed by timed intercrosses and embryonic phenotyping. Analyses of reproductive trends, viability, frequency of gene transmission, and fetal growth were performed, and supported that Slc20a2 deficient mice are subviable. Maternal health was monitored, and placental gene expression and anatomy were analyzed. Abnormal vascular morphology and a remarkable level of placental calcification (deposition of phosphate and calcium-containing mineral) associated with poor maternal health was observed in the Slc20a2 deficient placentas. These data provide the first molecular and histological insights into how Slc20a2 deficiency and dysfunctional phosphate transport may contribute to preeclampsia. Furthermore, we investigated Slc20a2 protein localization and placental calcification patterns in human placenta, and identified correlations with specific types of placental insufficiency. Our findings establish the first-ever placental calcification animal model, and direct our attention to the need to understand the impact that placental calcification has on placental pathophysiology.