Four Markers Useful for the Distinction of Intrauterine Growth Restriction in Sheep

SIMPLE SUMMARY: Intrauterine growth restriction (IUGR) is a disruption in the development of animal embryos or fetal organs in the maternal uterus and is highly regarded because of its serious detrimental effects on animal husbandry. However, there are few diagnostic methods and treatment options for IUGR, and its molecular mechanisms are not fully understood. In this study, a bioinformatics approach was applied to identify four IUGR-related diagnostic genes (IUGR-DGs) in sheep, construct a gene scoring system based on the IUGR-DGs, and evaluate the relationship between the IUGR score and disease risk. A new artificial neural network model was constructed to better diagnose the occurrence of IUGR in sheep based on the four IUGR-DGs. Although future studies will be necessary to elucidate the entire molecular mechanisms involved, we believe that the findings of this paper will facilitate the diagnosis and treatment of IUGR in sheep and improve livestock production levels. ABSTRACT: Intrauterine growth restriction (IUGR) is a common perinatal complication in animal reproduction, with long-lasting negative effects on neonates and postnatal animals, which seriously negatively affects livestock production. In this study, we aimed to identify potential genes associated with the diagnosis of IUGR through bioinformatics analysis. Based on the 73 differentially expressed related genes obtained by differential analysis and weighted gene co-expression network analysis, we used three machine learning algorithms to identify 4 IUGR-related hub genes (IUGR-HGs), namely, ADAM9, CRYL1, NDP52, and SERPINA7, whose ROC curves showed that they are a good diagnostic target for IUGR. Next, we identified two molecular subtypes of IUGR through consensus clustering analysis and constructed a gene scoring system based on the IUGR-HGs. The results showed that the IUGR score was positively correlated with the risk of IUGR. The AUC value of IUGR scoring accuracy was 0.970. Finally, we constructed a new artificial neural network model based on the four IUGR-HGs to diagnose sheep IUGR, and its accuracy reached 0.956. In conclusion, the IUGR-HGs we identified provide new potential molecular markers and models for the diagnosis of IUGR in sheep; they can better diagnose whether sheep have IUGR. The present findings provide new perspectives on the diagnosis of IUGR.