Prenatal Skeletal Muscle Transcriptome Analysis Reveals Novel MicroRNA-mRNA Networks Associated with Intrauterine Growth Restriction in Pigs

Abstract

Intrauterine growth restriction (IUGR) occurs in 15–20% of pig neonates and poses huge economic losses to the pig industry. IUGR piglets have reduced skeletal muscle growth, which may persist after birth. Prenatal muscle growth is regulated by complex molecular pathways that are not well understood. MicroRNAs (miRNAs) have emerged as the main regulators of vital pathways and biological processes in the body. This study was designed to identify miRNA–mRNA networks regulating prenatal skeletal muscle development in pigs. We performed an integrative miRNA–mRNA transcriptomic analysis in longissimus dorsi muscle from IUGR fetuses and appropriate for gestational age (AGA) fetuses at 63 days post conception. Our data showed that 47 miRNAs and 3257 mRNAs were significantly upregulated, and six miRNAs and 477 mRNAs were significantly downregulated in IUGR compared to AGA fetuses. Moreover, 47 upregulated miRNAs were negatively correlated and can potentially target 326 downregulated genes, whereas six downregulated miRNAs were negatively correlated and can potentially target 1291 upregulated genes. These miRNA–mRNA networks showed enrichment in biological processes and pathways critical for fetal growth, development, and metabolism. The miRNA–mRNA networks identified in this study can potentially serve as indicators of prenatal fetal growth and development as well as postnatal carcass quality.

In Utero Fetal Weight in Pigs Is Regulated by microRNAs and Their Target Genes

“…The breeding plan of animals and study design has been previously described [12]. Briefly, an F1 population was generated by crossbreeding DL and Pi breeds.…”

“…These animals were not subjected to any experimental treatment before slaughtering. LDM tissue was snap frozen in liquid nitrogen immediately after collection, and then transferred to −80 • C. Data from 12 F2 fetuses categorized as intrauterine growth restricted (IUGR) and 12 F2 fetuses categorized as appropriate for gestational age (AGA) have been recently published as a comparative study [12]. In the current study, the transcriptomic data from LDM of all 118 F2 fetuses were analyzed to identify miRNAs and genes correlated to fetal weight at 63 dpc.…”

“…We previously selected 12 fetuses representing an extreme for intrauterine growth restricted (IUGR) and 12 as appropriate for gestational age (AGA) [12]. We reported that miRNAs from 33 families were upregulated in LDM from IUGR fetuses, and were potentially involved in the pathogenesis of IUGR.…”

“…In a recent study, we established an F2 population by crossbreeding Pi and DL breeds and performed a transcriptomic analysis in LDM of fetuses at 63 dpc and identified novel miRNA-mRNA networks involved in pathogenesis of IUGR. We reported that 47 upregulated, 6 downregulated miRNAs, and their differentially expressed target genes in IUGR fetuses enriched several pathways and biological processes important for fetal growth and development [12]. In the current study, we used transcriptomic data from 118 F2 fetuses generated by crossbreeding of Pi and DL pigs to identify miRNAs and genes correlated with fetal weight at 63 dpc.…”

“…Multiple genes are targeted by a single miRNA and multiple miRNAs can target a single gene, which makes miRNAs a major player in gene regulation and important biological processes, including fetal and placental development [9][10][11]. Several studies have showed the role of miRNAs and their target genes in skeletal muscle development at different prenatal and postnatal stages across different breeds of pigs [7,[12][13][14][15][16][17].…”