Placental Calcification: Long-standing Questions and New Biomedical Research Directions

Abstract

The placenta is an essential organ that mediates interaction between maternal and fetal circulatory systems. The placenta is absolutely required for pregnancy and fetal growth, and placental disorders are associated with adverse maternal and fetal clinical outcomes. Placental calcification is characterized by calcium-phosphate mineral deposits in placental tissue, and placental calcification has been reported in association with adverse maternal and fetal clinical outcomes, including preterm birth, preeclampsia, and fetal growth restriction. Calcification in the placenta is observed in uncompleted pregnancies, increases with gestational age, and is a hallmark of viral infection. The biomedical significance of placental calcification and/or specific patterns or types of placental calcification remains incompletely understood. Careful experimental design, analysis, and data interpretation are required to study placental calcification. During pregnancy significant maternal hormonal adaptations mobilize minerals enabling unidirectional transport of essential minerals including calcium and phosphorus across the maternal-fetal interface. This process is promoted by active transport by calcium channels and phosphate transporters that move minerals against a concentration gradient at maternal-fetal interface to support embryonic accretion. Indeed, the recent identification of the sodium-dependent phosphate transporter Slc20a2 null mouse as a tractable animal model of placental calcification provides a genetic link and suggests that calcification may be actively regulated and/or programmed throughout gestation. Herein we review studies examining the relationship between placental calcification and clinical outcomes, observed mineral deposits in the placenta, mechanisms of calcium and phosphate homeostasis during pregnancy, and lessons learned about pro- and anti-calcific signaling from both clinical studies and animal models. In closing, we expand on how placental calcification is currently assessed clinically and discuss new frontiers in computer vision and image analysis, which may generate greater confidence in the ability to consider placental calcification in the interpretation of placental disorders.