Muscle Growth and Development in Intrauterine Growth Restricted Pigs
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Intrauterine growth restriction causes impaired growth and development of mammalian fetus, and leads to long-term negative effect on postnatal growth. Among domestic animals, pigs exhibit the most severe naturally occurring IUGR and reduced postnatal muscle growth. The objectives of this research project were to: 1) determine muscle stem cell characteristics in IUGR pigs; 2) determine how intrauterine growth restriction alters protein deposition in skeletal muscle; 3) investigate whether branched-chain amino acids (BCAA) are able to enhance protein synthesis in intrauterine growth restricted (IUGR) pig muscle. Newborn piglets were considered normal body weight (NBWT) or IUGR when birth weight was within ± 0.5 SD and -2 SD of litter average respectively. Muscle satellite cell numbers, believed to be the major nuclei source for postnatal muscle growth, were lower in newborn IUGR pigs which could result in reduced muscle hypertrophy potential. In addition, cultures derived from IUGR muscle satellite cells had a lower fusion percentage. Fewer satellite cells and impaired differentiation ability may contributor to impaired muscle growth in these pigs. Protein synthesis rate was significantly lower in IUGR pig hindquarter in the first hour after feeding, but BCAA supplementation had no effect on protein synthesis in IUGR pigs. Further, eukaryotic translation initiation factor 4E (eIF4E) expression is down regulated in IUGR pig muscle. These results suggest that impaired translation initiation may provide a plausible explanation for the lower protein synthesis rates observed in IUGR pigs. Overall, reduced muscle stem cell number and changes in their activity, as well as impaired translation initiation may be important explanations for compromised postnatal muscle growth in intrauterine growth restricted pigs.
- Doctoral Dissertations