Excessive backfat of sows at mating promotes oxidative stress and up-regulates mitochondrial-mediated apoptotic pathway in the full-term placenta

Abstract

The objective of this investigation was to evaluate the influence of back-fat thickness (BF), at mating of sows, on the placental oxidative stress, mitochondrial injury and apoptosis. For that purpose, we performed iTRAQ labeling based proteomic analysis on term placentas obtained by vaginal delivery from BFI (15–20 mm) and BFII (21–27 mm) sows formed according to BF at mating. Proteomic analysis revealed 413 proteins to be significantly different in placenta from BFII sows by ≥1.2-fold. Gene ontology (GO) analysis identified proteins related to oxidative stress response and apoptotic process to be altered in placenta from BFII sows. Indicative of increased oxidative stress and impaired mitochondrial function, higher placental MDA, H2O2 and O2− levels and reduced CAT and SOD activities were linked to decreased mitochondrial membrane potential and reduced mitochondrial DNA copy number and increased MPTP opening activity in placenta from BFII group (P< 0.05). Furthermore, a TUNEL apoptosis assay showed that increased back-fat triggered a 33% increase of apoptotic cells in placental villi; and apoptosis was confirmed by the decreased protein contents of Bcl-2, as well as the increased expression of Bax, cytochrome c, Apaf-1, caspase 9 and cleaved caspase 3 in placenta from BFII sows that was associated with higher caspase 3 activity (P< 0.05), suggesting the activation of mitochondrial apoptotic pathway. Excessive back-fat was also associated with increased activation of Mark4 and JNK1 and reduced activation of p38 MAPK in pig term placenta, suggesting the potential mechanisms underlying increased oxidative stress and apoptosis in placenta from BFII sows. Together, these findings indicate that excessive back-fat of sows at mating leads to increased oxidative stress that is associated with mitochondrial dysfunction and augmented apoptosis in the full-term placenta.