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

Asghar Ali,Xuan Liu,Klaus Wimmers,Eduard Murani,Frieder Hadlich,Siriluck Ponsuksili

doi:10.3390/cells10051007

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.

Highlights

Pig breeding programs have been traditionally focused on increasing litter size at birth and weaning [1,2]
Using the above described criteria, fetuses collected at 63 dpc were divided in two groups—intrauterine growth restricted fetuses (IUGR; n = 12) and appropriate for gestational age fetuses (AGA; n = 12)
Our analysis showed that six downregulated miRNAs can target 1291 upregulated genes, which are negatively correlated to these miRNAs

Summary

Introduction

Pig breeding programs have been traditionally focused on increasing litter size at birth and weaning [1,2]. Increased litter size affects litter uniformity, resulting in natural intrauterine growth restriction (IUGR) in some piglets [2]. IUGR is defined as the inability of a fetus to reach its maximum growth potential, resulting in a fetal or birth weight more than two standard deviations (SD) below the mean weight for the corresponding gestational age or mean weight of littermates [4,5]. IUGR in pigs is associated with high morbidity and mortality during perinatal and pre-weaning periods, and can lead to long term growth retardation and poor carcass quality [4,7,8]. Along with impaired growth and development of embryo/fetus, IUGR can affect multiple fetal tissues and organ systems [4]. A recent study has shown that IUGR in piglets affects the structure, proliferation, and differentiation of skeletal muscle fibers [11]

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