Effects Of Intrauterine Growth Restriction On Protein Expression Profiling Of The Growth And Metabolism In The Liver Of Newborn Piglets

Intrauterine growth restriction refers to impair the growth and development of the mammalian embryo or fetus and its organ during the pregnancy. In the animal production, 15-20% of newborn piglets with low birth weight are suffered by IUGR. IUGR newborn piglets have high morbidity and mortality, low efficiency of feed utilization, negatively affected meat quality, and health in postnatal life. So, IUGR causes serious losses to livestock production. Liver is a major organ of nutrient absorption and metabolism, whereas IUGR can impair hepatic growth and development. The weight of liver is reduced by IUGR compared with normal weight fetuses. Besides, IUGR fetal livers are accompanied by metabolic disorders in postnatal life, such as reduced oxidative phosphorylation and impaired mitochondrial function. Thereby, further extending the characterization of the mechanism underlying liver development and metabolism altered by IUGR will allow us to find the suitable therapeutic strategies.In this study, we applied iTRAQ to systematically investigate the distinction of liver proteome between IUGR and NW newborn piglets. We can comprehensively understand the key proteins and pathways which are related to IUGR formation. A total of three biological replicates of fetal livers from NW and IUGR were used to perform iTRAQ. Our results showed that a total of 2689, 2666, and 2669 proteins were quantified in the three biological replicates, respectively. Among them, 2635 proteins were common in all three biological replicates. As a result, there were 517, 359, and 191 differentially expressed proteins in the three biological replicates, respectively. Additionally, to avoid missing the differentially expressed proteins, we selected candidate proteins that were significantly changed in at least two replicates and simultaneously in anther replicates conformed to this variation trend. Ultimately, 78 proteins were considered as candidate proteins, including 31 significantly up-regulated proteins and 47 significantly down-regulated proteins. Functional classification analysis of these differentially expressed proteins reveals that these differentially expressed proteins were involved in carbohydrate metabolism, protein synthesis, energy production and the development of organ. Pathway analysis showed that some pathways associated with protein synthesis with lower p value were inhibited by IUGR in the liver of newborn piglets, such as EIF2 signaling, regulation of eIF4 and p70S6 K signaling, and mTOR signaling. Phagosome maturation, which is related to autophagy, was also inhibited by IUGR. Additionally, the pathways related to nutrient metabolism were affectedly by IUGR, such as tryptophan degradation, lanosterol biosynthesis, choline degradation, and oxidative phosphorylation. The results of network analysis showed that these 78 differentially expressed proteins were distributed in five networks. These networks were associated with development disorder and nutrient metabolism(lipid metabolism and energy production). PP2 Ac, a significantly down-regulated protein in IUGR newborn piglets, appeared in the above network. Previous studies have reported that PP2 Ac is related to early embryonic development, glucose metabolism, and autophagy. Our results showed that under glucose deprivation, PP2 Ac inhibition can significantly activate AMPK and reduce autophagy in HepG2 cells. Thereby, the down-regulation of PP2 Ac may be one of the key factors in affecting the growth and development of liver and inhibiting the autophagy induced by glucose deprivation in IUGR newborn piglets.In summary, we obtain the following conclusions:(1) the pathways related to nutrient metabolism are affected by IUGR, such as energy production and lipid metabolism.(2) Protein synthesis pathways are suppressed in the liver of IUGR newborn piglets.(3) Autophagy is inhibited in the liver of IUGR newborn piglets.(D) PP2 Ac may be one of the key factors in affecting the growth and development of liver and inhibiting the autophagy induced by glucose deprivation in IUGR newborn piglets.