Journal
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
Volume 322, Issue 3, Pages R228-R240Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpregu.00222.2021
Keywords
fetal growth restriction; fetal programming; fi ber type; mitochondria; nucleotides
Categories
Funding
- Ludeman Family Center for Women's Health Research at the University of Colorado Anschutz Medical Center [R01 HD079404]
- Department of Veterans Affairs [BX002046, CX001532]
- Ludeman Family Center for Women's Health Research
- [UL1 TR002535]
- [R01-DK108910]
- [R01-DK-124344]
- [P30-DK-116073]
- [UL1-TR-001082]
- [R01-AG-066562]
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There is evidence of reduced oxidative phosphorylation in skeletal muscle from sheep fetuses with intrauterine growth restriction (IUGR) due to intrinsic deficits in mitochondrial respiration. Mitochondrial respiration is similar in control and IUGR muscle fibers, but IUGR muscle has lower citrate synthase activity, lower protein expression of individual mitochondrial complex subunits, and lower expression of type I oxidative fibers.
Skeletal muscle from the late gestation sheep fetus with intrauterine growth restriction (IUGR) has evidence of reduced oxidative metabolism. Using a sheep model of placental insufficiency and IUGR, we tested the hypothesis that by late gestation, IUGR fetal skeletal muscle has reduced capacity for oxidative phosphorylation because of intrinsic deficits in mitochondrial respiration. We measured mitochondrial respiration in permeabilized muscle fibers from biceps femoris (BF) and soleus (SOL) from control and IUGR fetal sheep. Using muscles including BF, SOL, tibialis anterior (TA), and flexor digitorum superficialis (FDS), we measured citrate synthase (CS) activity, mitochondrial complex subunit abundance, fiber type distribution, and gene expression of regulators of mitochondrial biosynthesis. Ex vivo mitochondrial respiration was similar in control and IUGR muscle. However, CS activity was lower in IUGR BF and TA, indicating lower mitochondrial content, and protein expression of individual mitochondrial complex subunits was lower in IUGR TA and BF in a muscle-specific pattern. IUGR TA, BF, and FDS also had lower expression of type I oxidative fibers. Fiber-type shifts that support glycolytic instead of oxidative metabolism may be advantageous for the IUGR fetus in a hypoxic and nutrient-deficient environment, whereas these adaptions may be maladaptive in postnatal life.
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