The balancing act - PPAR-γ's roles at the maternal-fetal interface

Peroxisome proliferator-activated receptor-gamma (PPAR-γ) belongs to the nuclear hormone receptor superfamily. Apart from being involved in lipid metabolism, like its other subtypes PPAR α and β, it is implicated to be crucial for successful placentation. While its role in extravillous trophoblast (EVT) differentiation has been studied, the involvement in villous trophoblast (VT) differentiation, fatty-acid metabolism, inflammatory responses, and oxidative pathways during pregnancy deserves more attention. PPAR-γ's potential role in balancing structural development and functional responsibilities at the maternal-fetal interface suggest a more central role for the receptor. The central role of PPAR-γ in pathways related to placental pathologies suggests a potential role of PPAR-γ in placental function. The molecular regulation of PPAR-γ in this context has been widely disregarded. In this review, we discuss the less explored functions of PPAR-γ in the areas of immunological responses and management of oxidative stress in the placenta. We also shed light on the involvement of PPAR-γ in pathologic pregnancies and briefly discuss the current models in the field. The ability to modulate PPAR-γ's activity using already available drugs makes it a tempting therapeutic target. Elucidation of the molecular pathways and specific targets regulated by PPAR-γ will provide more information on the role of PPAR-γ in placentation and related disorders in pregnancy. Furthermore it will close the critical gap in our knowledge about the differential regulation of PPAR-γ in the two trophoblast lineages. This will help to evaluate the usefulness and timing of PPAR-γ modulation in at risk pregnancies to improve placental and endothelial function.