Anemic Hypoxemia Reduces Myoblast Proliferation and Muscle Growth in Late Gestation Fetal Sheep

2021 ◽  
Author(s):  
Paul J. Rozance ◽  
Stephanie R Wesolowski ◽  
Sonnet S. Jonker ◽  
Laura D Brown
Keyword(s):  
Skeletal Muscle ◽  
Mrna Expression ◽  
Muscle Growth ◽  
Late Gestation ◽  
Whole Body ◽  
Myoblast Differentiation ◽  
Fetal Sheep ◽  
Body Protein ◽  
Skeletal Muscle Growth ◽  
Myoblast Proliferation

Fetal skeletal muscle growth requires myoblast proliferation, differentiation, and fusion into myofibers in addition to protein accretion for fiber hypertrophy. Oxygen is an important regulator of this process. Therefore, we hypothesized that fetal anemic hypoxemia would inhibit skeletal muscle growth. Studies were performed in late gestation fetal sheep that were bled to anemic, and therefore hypoxemic, conditions beginning at ~125 days of gestation (term = 148 days) for 9 ± 0 days (n=19) and compared to control fetuses (n=16). A metabolic study was performed on gestational day ~134 to measure fetal protein kinetic rates. Myoblast proliferation and myofiber area were determined in biceps femoris (BF), tibialis anterior (TA), and flexor digitorum superficialis (FDS) muscles. mRNA expression of muscle regulatory factors was determined in BF. Fetal arterial hematocrit and oxygen content were 28% and 52% lower, respectively, in anemic fetuses. Fetal weight and whole-body protein synthesis, breakdown, and accretion rates were not different between groups. Hindlimb length, however, was 7% shorter in anemic fetuses. TA and FDS muscles weighed less and FDS myofiber area was smaller in anemic fetuses compared to controls. The percentage of Pax7+ myoblasts that expressed Ki67 was lower in BF and tended to be lower in FDS from anemic fetuses indicating reduced myoblast proliferation. There was less MYOD and MYF6 mRNA expression in anemic vs. control BF consistent with reduced myoblast differentiation. These results indicate that fetal anemic hypoxemia reduced muscle growth. We speculate that fetal muscle growth may be improved by strategies that increase oxygen availability.

scholarly journals Chronic Hyperinsulinemia Increases Myoblast Proliferation in Fetal Sheep Skeletal Muscle

Endocrinology ◽  
2016 ◽  
Vol 157 (6) ◽  
pp. 2447-2460 ◽  
Author(s):  
Laura D. Brown ◽  
Stephanie R. Wesolowski ◽  
Jenai Kailey ◽  
Stephanie Bourque ◽  
Averi Wilson ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Lean Mass ◽  
Biceps Femoris ◽  
Late Gestation ◽  
Muscle Size ◽  
Substrate Uptake ◽  
Ki 67 ◽  
Fetal Sheep ◽  
Umbilical Blood ◽  
Myoblast Proliferation

Insulin is an important fetal growth factor. However, chronic experimental hyperinsulinemia in the fetus fails to accelerate linear and lean mass growth beyond normal rates. Mechanisms preventing accelerated lean mass accretion during hyperinsulinemia are unknown. To address potential mechanisms, late-gestation fetal sheep were infused with iv insulin and glucose to produce euglycemic hyperinsulinemia (INS) or saline for 7–9 days. Fetal substrate uptake and protein metabolic rates were measured. INS fetuses had 1.5-fold higher insulin concentrations (P < .0001) and equivalent glucose concentrations. INS fetuses had 20% more Pax7+ nuclei in the biceps femoris, which indicates the potential for hyperinsulinemia to increase the number of myoblasts within late-gestation fetal skeletal muscle. Additionally, the percentage of Pax7+ myoblasts that expressed Ki-67 was 1.3-fold higher and expression of myogenic regulatory factors was 50% lower in INS fetuses (MYF5 and MYOG [myogenin], P < .005), which indicates a shift toward myoblast proliferation over differentiation. There were no differences for fetal body, organ, or muscle weights, although INS placentas weighed 28% less (P < .05). Protein synthesis and accretion rates did not change in INS fetuses, nor did fiber muscle size. Essential amino acid concentrations were lower in the INS group (P < .05) except for tryptophan. Umbilical blood flow, net total amino acids, and O2 uptakes rates did not differ between groups. Arterial O2 content was 33% lower (P < .005) and norepinephrine was 100% higher in the INS fetuses (P < .01), all of which are factors that may counteract fetal protein accretion during hyperinsulinemia despite an increase in myoblast proliferation.

scholarly journals Analysis of dynamic and widespread lncRNA and miRNA expression in fetal sheep skeletal muscle

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9957
Author(s):  
Chao Yuan ◽  
Ke Zhang ◽  
Yaojing Yue ◽  
Tingting Guo ◽  
Jianbin Liu ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Development ◽  
Expression Profiles ◽  
Muscle Growth ◽  
Skeletal Muscle Development ◽  
Fetal Sheep ◽  
Lncrna Gene ◽  
Skeletal Muscle Growth ◽  
Wide Range ◽  
Non Coding Rnas

The sheep is an economically important animal, and there is currently a major focus on improving its meat quality through breeding. There are variations in the growth regulation mechanisms of different sheep breeds, making fundamental research on skeletal muscle growth essential in understanding the regulation of (thus far) unknown genes. Skeletal muscle development is a complex biological process regulated by numerous genes and non-coding RNAs, including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). In this study, we used deep sequencing data from sheep longissimus dorsi (LD) muscles sampled at day 60, 90, and 120 of gestation, as well as at day 0 and 360 following birth, to identify and examine the lncRNA and miRNA temporal expression profiles that regulate sheep skeletal myogenesis. We stained LD muscles using histological sections to analyse the area and circumference of muscle fibers from the embryonic to postnatal development stages. Our results showed that embryonic skeletal muscle growth can be characterized by time. We obtained a total of 694 different lncRNAs and compared the differential expression between the E60 vs. E90, E90 vs. E120, E120 vs. D0, and D0 vs. D360 lncRNA and gene samples. Of the total 701 known sheep miRNAs we detected, the following showed a wide range of expression during the embryonic stage: miR-2387, miR-105, miR-767, miR-432, and miR-433. We propose that the detected lncRNA expression was time-specific during the gestational and postnatal stages. GO and KEGG analyses of the genes targeted by different miRNAs and lncRNAs revealed that these significantly enriched processes and pathways were consistent with skeletal muscle development over time across all sampled stages. We found four visual lncRNA–gene regulatory networks that can be used to explore the function of lncRNAs in sheep and may be valuable in helping improve muscle growth. This study also describes the function of several lncRNAs that interact with miRNAs to regulate myogenic differentiation.

Identification of amino acids associated with skeletal muscle growth in late gestation and at weaning in lambs of well-nourished sheep1

2014 ◽  
Vol 92 (11) ◽  
pp. 5041-5052 ◽  
Author(s):  
F. A. Sales ◽  
D. Pacheco ◽  
H. T. Blair ◽  
P. R. Kenyon ◽  
G. Nicholas ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Amino Acids ◽  
Muscle Growth ◽  
Late Gestation ◽  
Skeletal Muscle Growth

scholarly journals Genome-Wide Identification, Characterization and Expression Profiling of myosin Family Genes in Sebastes schlegelii

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 808
Author(s):  
Chaofan Jin ◽  
Mengya Wang ◽  
Weihao Song ◽  
Xiangfu Kong ◽  
Fengyan Zhang ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Molecular Mechanisms ◽  
Expression Patterns ◽  
Muscle Growth ◽  
Myoblast Differentiation ◽  
Growth Stages ◽  
Marine Teleost ◽  
Black Rockfish ◽  
Skeletal Muscle Growth ◽  
Sebastes Schlegelii

Myosins are important eukaryotic motor proteins that bind actin and utilize the energy of ATP hydrolysis to perform a broad range of functions such as muscle contraction, cell migration, cytokinesis, and intracellular trafficking. However, the characterization and function of myosin is poorly studied in teleost fish. In this study, we identified 60 myosin family genes in a marine teleost, black rockfish (Sebastes schlegelii), and further characterized their expression patterns. myosin showed divergent expression patterns in adult tissues, indicating they are involved in different types and compositions of muscle fibers. Among 12 subfamilies, S. schlegelii myo2 subfamily was significantly expanded, which was driven by tandem duplication events. The up-regulation of five representative genes of myo2 in the skeletal muscle during fast-growth stages of juvenile and adult S. schlegelii revealed their active role in skeletal muscle fiber synthesis. Moreover, the expression regulation of myosin during the process of myoblast differentiation in vitro suggested that they contribute to skeletal muscle growth by involvement of both myoblast proliferation and differentiation. Taken together, our work characterized myosin genes systemically and demonstrated their diverse functions in a marine teleost species. This lays foundation for the further studies of muscle growth regulation and molecular mechanisms of indeterminate skeletal muscle growth of large teleost fishes.

scholarly journals Guanidinoacetic Acid Regulates Myogenic Differentiation and Muscle Growth Through miR-133a-3p and miR-1a-3p Co-mediated Akt/mTOR/S6K Signaling Pathway

2018 ◽  
Vol 19 (9) ◽  
pp. 2837 ◽  
Author(s):  
Yujie Wang ◽  
Jideng Ma ◽  
Wanling Qiu ◽  
Jinwei Zhang ◽  
Siyuan Feng ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Mrna Expression ◽  
Signaling Pathway ◽  
Myogenic Differentiation ◽  
Muscle Growth ◽  
Luciferase Reporter ◽  
Amino Acid Derivative ◽  
Cyclin Dependent Kinase ◽  
Skeletal Muscle Growth ◽  
Guanidinoacetic Acid

Guanidinoacetic acid (GAA), an amino acid derivative that is endogenous to animal tissues including muscle and nerve, has been reported to enhance muscular performance. MicroRNA (miRNA) is a post-transcriptional regulator that plays a key role in nutrient-mediated myogenesis. However, the effects of GAA on myogenic differentiation and skeletal muscle growth, and the potential regulatory mechanisms of miRNA in these processes have not been elucidated. In this study, we investigated the effects of GAA on proliferation, differentiation, and growth in C2C12 cells and mice. The results showed that GAA markedly inhibited the proliferation of myoblasts, along with the down-regulation of cyclin D1 (CCND1) and cyclin dependent kinase 4 (CDK4) mRNA expression, and the upregulation of cyclin dependent kinase inhibitor 1A (P21) mRNA expression. We also demonstrated that GAA treatment stimulated myogenic differentiation 1 (MyoD) and myogenin (MyoG) mRNA expression, resulting in an increase in the myotube fusion rate. Meanwhile, GAA supplementation promoted myotube growth through increase in total myosin heavy chain (MyHC) protein level, myotubes thickness and gastrocnemius muscle cross-sectional area. Furthermore, small RNA sequencing revealed that a total of eight miRNAs, including miR-133a-3p and miR-1a-3p cluster, showed differential expression after GAA supplementation. To further study the function of miR-133a-3p and miR-1a-3p in GAA-induced skeletal muscle growth, we transfected miR-133a-3p and miR-1a-3p mimics into myotube, which also induced muscle growth. Through bioinformatics and a dual-luciferase reporter system, the target genes of miR-133a-3p and miR-1a-3p were determined. These two miRNAs were shown to modulate the Akt/mTOR/S6K signaling pathway by restraining target gene expression. Taken together, these findings suggest that GAA supplementation can promote myoblast differentiation and skeletal muscle growth through miR-133a-3p- and miR-1a-3p-induced activation of the AKT/mTOR/S6K signaling pathway.

Effect of rhIGF-I infusion on whole fetal and fetal skeletal muscle protein metabolism in sheep

1998 ◽  
Vol 275 (6) ◽  
pp. E1082-E1091 ◽  
Author(s):  
David W. Boyle ◽  
Scott C. Denne ◽  
Helen Moorehead ◽  
Wei-Hua Lee ◽  
Ronald R. Bowsher ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Metabolism ◽  
Muscle Protein ◽  
External Iliac Artery ◽  
Late Gestation ◽  
Whole Body ◽  
Skeletal Muscle Protein ◽  
Fetal Sheep ◽  
Igf I ◽  
Body Level

Insulin-like growth factor I (IGF-I) has been shown to have significant anabolic effects in the regulation of fetal protein metabolism. To investigate the tissue-specific effects of IGF-I on fetal skeletal muscle metabolism, we infused recombinant human (rh) IGF-I directly into the hindlimb of nine chronically catheterized, late-gestation fetal sheep. Substrate balance and amino acid kinetics were measured across the hindlimb and were compared with the effects at the whole body level before and during a 3-h infusion of rhIGF-I into the external iliac artery at 150 μg/h. Infusion of rhIGF-I resulted in increases in IGF-I concentrations by 2- to 5.75-fold in the ipsilateral iliac vein and by nearly 3-fold in the abdominal aorta. In the study limb, IGF-I had no effect on protein synthesis (phenylalanine rate of disposal 0.88 ± 0.13 before vs. 0.73 ± 0.19 μmol/min during IGF-I) or breakdown (phenylalanine rate of appearance 0.67 ± 0.13 before vs. 0.60 ± 0.17 μmol/min during IGF-I) and did not alter net phenylalanine balance. IGF-I also did not affect hindlimb oxygen or glucose uptake. In contrast, at the whole body level, the rate of appearance of leucine, indicative of fetal protein breakdown, decreased during IGF-I infusion (rate of appearance of leucine 41.1 ± 3.3 to 37.6 ± 2.7 μmol/min) as did fetal leucine oxidation (8.4 ± 0.8 to 6.8 ± 0.6 μmol/min). There was no change in the umbilical uptake of leucine, and although not statistically significant, fetal leucine accretion increased 2.4-fold. These results provide further evidence that IGF-I promotes fetal protein accretion; however, its site of action is in tissues other than skeletal muscle.

scholarly journals Dietary supplementation of β-guanidinopropionic acid (βGPA) reduces whole-body and skeletal muscle growth in young CD-1 mice

2015 ◽  
Vol 403 (1-2) ◽  
pp. 277-285 ◽  
Author(s):  
Bradley L. Baumgarner ◽  
Alison M. Nagle ◽  
Meagan R. Quinn ◽  
A. Elaine Farmer ◽  
Stephen T. Kinsey
Keyword(s):  
Skeletal Muscle ◽  
Muscle Growth ◽  
Dietary Supplementation ◽  
Whole Body ◽  
Skeletal Muscle Growth

Sexually dimorphic changes in the pancreas and skeletal muscle in young adulthood following intra-amniotic IGF-I treatment of growth-restricted fetal sheep

2021 ◽  
Author(s):  
Emma Jane Buckels ◽  
Frank Harry Bloomfield ◽  
Mark Hope Oliver ◽  
Ana-Mishel Spiroski ◽  
Jane Elizabeth Harding ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Mrna Expression ◽  
Young Adulthood ◽  
Endocrine Pancreas ◽  
Cell Mass ◽  
Late Gestation ◽  
Control Group ◽  
Sexually Dimorphic ◽  
Fetal Sheep ◽  
Igf I

Fetal growth restriction (FGR) is associated with decreased insulin secretory capacity and decreased insulin sensitivity in muscle in adulthood. We investigated whether intra-amniotic IGF-I treatment in late gestation mitigated the adverse effects of FGR on the endocrine pancreas and skeletal muscle at 18-months of age. Singleton-bearing ewes underwent uterine artery embolization between 103-107 days' gestational age, followed by five once-weekly intra-amniotic injections of 360 µg IGF-I (FGRI) or saline (FGRS), and were compared to an un-manipulated control group (CON). We measured offspring pancreatic endocrine cell mass and pancreatic and skeletal muscle mRNA expression at 18-months of age (n=7-9/sex/group). Total α-cell mass was increased ~225% in FGRI males vs. CON and FGRS males, while β-cell mass was not different between groups of either sex. Pancreatic mitochondria-related mRNA expression was increased in FGRS females vs. CON (NRF1, MTATP6, UCP2), and FGRS males vs. CON (TFAM, NRF1, UCP2), but was largely unchanged in FGRI males vs. CON. In skeletal muscle, mitochondria-related mRNA expression was decreased in FGRS females vs. CON (PPARGC1A, TFAM, NRF1, UCP2, MTATP6), FGRS males vs. CON (NRF1 and UCP2), and FGRI females vs. CON (TFAM and UCP2), with only MTATP6 expression decreased in FGRI males vs. CON. Although the window during which IGF-I treatment was delivered was limited to the final five weeks of gestation, IGF-I therapy of FGR altered the endocrine pancreas and skeletal muscle in a sex-specific manner in young adulthood.

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