Life Sciences Commons^™

Maternal Inflammation At Midgestation Impairs Subsequent Fetal Myoblast Function And Skeletal Muscle Growth In Rats, Resulting In Intrauterine Growth Restriction At Term, Caitlin N. Cadaret, Robert J. Posont, Kristin A. Beede, Hannah E. Riley, John Dustin Loy, Dustin T. Yates

Department of Animal Science: Faculty Publications

Maternal inflammation induces intrauterine growth restriction (MI-IUGR) of the fetus, which compromises metabolic health in human offspring and reduces value in livestock. The objective of this study was to determine the effect of maternal inflammation at midgestation on fetal skeletal muscle growth and myoblast profiles at term. Pregnant Sprague-Dawley rats were injected daily with bacterial endotoxin (MI-IUGR) or saline (controls) from the 9th to the 11th day of gestational age (dGA; term = 21 dGA). At necropsy on dGA 20, average fetal mass and upper hindlimb cross-sectional areas were reduced (P < 0.05) in MI-IUGR fetuses compared with controls. MyoD+ and myf5+ myoblasts were less abundant (P < 0.05), and myogenin+ myoblasts were more abundant (P < 0.05) in MI-IUGR hindlimb skeletal muscle compared with controls, indicating precocious myoblast differentiation. Type I and Type II hindlimb muscle fibers were smaller (P < 0.05) in MI-IUGR fetuses than in controls, but fiber type proportions did not differ between experimental groups. Fetal blood plasma TNFα concentrations were below detectable amounts in both experimental groups, but skeletal muscle gene expression for the cytokine receptors TNFR1, IL6R, and FN14 was greater (P < 0.05) in MI-IUGR fetuses than controls, perhaps indicating enhanced sensitivity to these cytokines. Maternal blood glucose concentrations at term did not differ between experimental groups, but MI-IUGR fetal blood contained less (P < 0.05) glucose, cholesterol, and triglycerides. Fetal-to-maternal blood glucose ratios were also reduced (P < 0.05), which is indicative of placental insufficiency. Indicators of protein catabolism, including blood plasma urea nitrogen and creatine kinase, were greater (P < 0.05) in MI-IUGR fetuses than in controls. From these findings, we conclude that maternal inflammation at midgestation causes muscle-centric fetal programming that impairs myoblast function, increases protein catabolism, and reduces skeletal muscle growth near term. Fetal muscle sensitivity to inflammatory cytokines appeared to be enhanced after maternal inflammation, which may represent a mechanistic target for improving these outcomes in MI-IUGR fetuses.

Real Supermodels Wear Wool: Summarizing The Impact Of The Pregnant Sheep As An Animal Model For Adaptive Fetal Programming, Kristin A. Beede, Sean W. Limesand, Jessica L. Petersen, Dustin T. Yates

Department of Animal Science: Faculty Publications

• Intrauterine growth restriction (IUGR) continues to be a global epidemic that is associated with high early-life mortality rates and greater risk for developing metabolic disorders that lower length and quality of life in affected individuals.

• Fetal programming of muscle growth and metabolic function associated with IUGR is often comparable among nonlitter bearing mammalian species, which allows much of the information learned in domestic animal models to be applicable to humans (and other animals).

• Recent studies in sheep models of IUGR have begun to uncover the molecular mechanisms linking adaptive fetal programming and metabolic dysfunction.

• Targets of …