The untapped potential of placenta-enriched molecules for diagnostic and therapeutic development.

Pregnancy complications such as fetal growth restriction and preeclampsia are diseases with limited biomarkers for prediction, and a complete lack of therapeutic options. We define placenta-enriched molecules as those that are highly expressed in the placenta relative to all other human tissues. Many exist including mRNAs, miRNAs and proteins. It is now well established that placenta-enriched mRNAs are found within the maternal circulation and are cleared rapidly after birth. Similarly, distinct clusters of miRNAs that are placenta-enriched have been identified and are measurable within the circulation. However, perhaps the most established potential diagnostics thus far are circulating placental proteins such as placental growth factor (PlGF), pregnancy associated pregnancy protein-A (PAPP-A) and soluble FMS-like tyrosine kinase 1 (sFlt-1). There has also been much interest in targeting placenta-enriched molecules as a means to treat diseases of pregnancy. We have shown promising results in targeting placenta-enriched epidermal growth factor receptor (EGFR) to treat ectopic pregnancy. Others have focused on using placenta-enriched molecules as a means of homing therapeutic-filled nanoparticles to the placenta, or to directly target sFlt-1 to improve disease outcomes. Importantly, many placenta-enriched molecules remain largely unstudied. We propose that a better understanding of their biology, and potential contribution to the pathogenesis of diseases, may yield more predictive diagnostic and therapeutic targets.