Differential proteomics of placentas reveals metabolic disturbance and oxidative damage participate yak spontaneous miscarriage during late pregnancy

Abstract

Background: High spontaneous miscarriage rate in yak, especially during late pregnancy, have caused a great economic loss to herdsmen living in the Qinghai-Tibet plateau. However, the mechanism underlying spontaneous miscarriage is still poorly understood. In the present study, placenta protein markers were identified to elucidate the pathological reasons for yak spontaneous miscarriage through isobaric tags for relative and absolute quantification (iTRAQ) proteomic technology and bioinformatic approaches.

Results: Subsequently, a total of 415 differentially expressed proteins (DEPs) were identified between aborted and normal placentas. The up-regulated DEPs in the aborted placentas were significantly associated with "spinocerebellar ataxia", "sphingolipid signalling", "relaxin signalling", "protein export", "protein digestion and absorption" and "aldosterone synthesis and secretion" pathway. While the down-regulated DEPs in the aborted placentas mainly participated in "valine, leucine and isoleucine degradation", "PPAR signalling", "peroxisome", "oxidative phosphorylation", "galactose metabolism", "fatty acid degradation", "cysteine and methionine metabolism" and "citrate cycle" pathway.

Conclusions: The results implied that the identified DEPs could be considered as placental protein markers for yak miscarriage during late pregnancy, and biomacromolecule metabolic abnormality and oxidative damage might be responsible for the high spontaneous miscarriage rate in yak. These findings provide an important theoretical basis for deciphering the pathologic mechanism of late spontaneous miscarriage in yak.

Keywords: Abortion; Metabolism; Oxidative stress; Placenta; Proteomics; Yak; iTRAQ.

Fig. 1

Expression status, principal component analysis (PCA) and heatmap of the total identified proteins in the yak placentas. (a) Pie chart shows the rate of identified peptide coverage; (b) Boxplot indicates the total protein expression in the different placenta samples; (c) PCA biplot exhibits the aggregation of the intragroup samples based on the first two principal components; (d) Heatmap demonstrates the global expression difference of the total proteins between the normal and aborted placenta samples

Fig. 2

Expression pattern of the differentially expressed proteins (DEPs) between the normal and abortive group. (a) Volcano plot illustrates the DEPs between the normal and abortive group; (b) Bar plot exhibits the numbers of the up- and down-regulated DEPs; (c) Heatmap demonstrates the DEP expression difference between the normal and aborted placenta samples

Fig. 3

Bubble diagrams of the gene ontology (GO) enrichment analysis for the differentially expressed proteins (DEPs) between the normal and abortive group. (a) Bubble diagram demonstrates that the up-regulated DEPs in the abortive group participate signal transduction, cellular response, extracellular structure organization and protein localization; (b) Bubble diagram manifests that the down-regulated DEPs in the abortive group take parts in lipid, protein and carbohydrate metabolic process and redox balance regulation

Fig. 4

Bubble diagrams of Kyoto encyclopaedia of genes and genomes (KEGG) pathway enrichment for the differentially expressed proteins (DEPs) between the normal and abortive group. (a) Bubble diagram demonstrates that the up-regulated DEPs participate in relaxin signal, protein metabolism and defend against pathogens; (b) Bubble diagram indicates that the down-regulated DEPs take parts in amino acid degradation, glycometabolism, lipid metabolism and redox balance

Fig. 5

Networks of protein to protein interaction (PPI) of the differentially expressed proteins (DEPs) screened by molecular complex detection (MCODE) plugin of the software Cytoscape. (a) Key PPI networks for the up-regulated DEPs in the aborted placentas; (b) Key PPI networks for the down-regulated DEPs in the aborted placentas