61: Maternal undernutrition induces fetal growth restriction by PPAR-mediated placental apoptosis

Abstract

Maternal undernutrition (MUN) during pregnancy results in growth restricted (IUGR) fetuses, in part a result of insufficient maternal nutrient supply. In addition, cell death (apoptosis) within the placenta may reduce the capacity for nutrient/oxygen transfer. We sought to determine if MUN induced placental apoptosis, and whether this may be mediated via dysregulation of pro (cytochrome) and anti (PPAR, Bc12) apoptotic factors. We analyzed the apoptotic index and protein expression of apoptotic mediators in the two placental positions with optimal and reduced nutrient/oxygen supply (proximal, mid-horn), and the placental zones associated with hormone production or feto-maternal exchange (basal, labyrinth). Pregnant rats were fed an AdLib diet or were 50% MUN starting at E10. At E20, left mid- and proximal horn apoptosis was measured with TUNEL assay. The corresponding right placentas were separated into basal and labyrinth zones and analyzed for PPAR, Bcl2 (anti-apoptotic protein) and cytochrome c (initiator of apoptotic process) expression. At E20, MUN maternal, fetal and placental (basal and labyrinth zones) weights were significantly decreased. MUN proximal placentas had markedly increased apoptosis in basal (3.3±1.0 vs 0.3±0.1%) and labyrinth (8.6±1.4 vs 0.6±0.3%) zones as compared to controls. Similarly, MUN mid-horn placentas showed greater degree of apoptosis in basal (5.5±0.2 vs. 0.7±0.1%) and labyrinth (10.1±1.1 vs. 0.13±0.07%) zones. Consistent with apoptosis, MUN placentas had reduced PPAR expression in both zones and positions whereas Bcl2 was downregulated in both zones, and cytochrome c was upregulated in the labyrinth zone. Downregulation of PPAR and Bcl2 together with upregulated cytochrome c may contribute to greater placental apoptosis in MUN pregnancies with subsequent deleterious effects on fetal growth.