TY - JOUR
T1 - Maternal inflammation at midgestation impairs subsequent fetal myoblast function and skeletal muscle growth in rats, resulting in intrauterine growth restriction at term
AU - Cadaret, Caitlin N.
AU - Posont, Robert J.
AU - Beede, Kristin A.
AU - Riley, Hannah E.
AU - Loy, John Dustin
AU - Yates, Dustin T.
N1 - Funding Information:
1This manuscript is based on research that was partially supported by the National Institute of General Medical Sciences Grant 1P20GM104320 (J. Zempleni, Director), the Nebraska Agricultural Experiment Station with funding from the Hatch Act (Accession Number 1009410) and Hatch Multistate Research capacity funding program (Accession Numbers 1011055, 1009410) through the USDA National Institute of Food and Agriculture. The Biomedical and Obesity Research Core (BORC) in the Nebraska Center
Funding Information:
This manuscript is based on research that was partially supported by the National Institute of General Medical Sciences Grant 1P20GM104320 (J. Zempleni, Director), the Nebraska Agricultural Experiment Station with funding from the Hatch Act (Accession Number 1009410) and Hatch Multistate Research capacity funding program (Accession Numbers 1011055, 1009410) through the USDA National Institute of Food and Agriculture. The Biomedical and Obesity Research Core (BORC) in the Nebraska Center for Prevention of Obesity Diseases (NPOD) receives partial support from NIH (NIGMS) COBRE IDeA award NIH 1P20GM104320. The contents of this publication are the sole responsibility of the authors and do not necessarily represent the official views of the NIH or NIGMS. The authors have no conflicts of interest to declare.
Funding Information:
for Prevention of Obesity Diseases (NPOD) receives partial support from NIH (NIGMS) COBRE IDeA award NIH 1P20GM104320. The contents of this publication are the sole responsibility of the authors and do not necessarily represent the official views of the NIH or NIGMS. The authors have no conflicts of interest to declare. 2Corresponding author: [email protected] Received February 4, 2019. Accepted March 29, 2019.
Publisher Copyright:
© The Author(s) 2019.
PY - 2019/2/26
Y1 - 2019/2/26
N2 - 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.
AB - 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.
KW - Adaptive fetal programming
KW - Developmental origins
KW - Inflammatory regulation
KW - Maternofetal stress
KW - Thrifty phenotype
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U2 - 10.1093/tas/txz037
DO - 10.1093/tas/txz037
M3 - Article
C2 - 31032478
AN - SCOPUS:85072332406
SN - 2573-2102
VL - 3
SP - 867
EP - 876
JO - Translational Animal Science
JF - Translational Animal Science
IS - 2
ER -