Increased Placental Apoptosis in Maternal Food Restricted Gestations: Role of the Fas Pathway

The placenta has a pivotal role, shuttling nutrients to the developing fetus and producing hormones essential to pregnancy. Maternal food restriction (MFR) during pregnancy results in growth restricted newborns, a consequence attributed primarily to maternal nutrient supply. We hypothesized that MFR further compromises fetal growth by decreased placental growth or increased placental apoptosis. We determined the potential pathway (Fas-Fas-ligand; Fas-FasL) of placental apoptosis in MFR pregnancies. We assessed the two morphologically and functionally distinct zones (basal and labyrinth) at embryonic age 20 (E20) in ad libitum fed controls (AdLib) and 50% MFR placentas. We studied fetuses and placentas from both proximal and mid-horn positions to evaluate any differential impact by MFR. Placenta apoptosis was quantified using terminal dUTP nick-end labeling (TUNEL) assay and the data were compared to immunodetection of cleaved caspase-3, Fas and FasL followed by Western blot quantification of Fas, FasL, caspase-8 and -3, tBID, and poly-ADP-ribose polymerase (PARP). MFR reduced maternal, fetal and placental basal and labyrinth weights. The results suggest that the increased apoptosis may be mediated, in part, via Fas pathway and the defective placental development in the MFR may be a major contributor to the decreased fetal growth.