title: Histological and transcriptome-wide level characteristics of fetal myofiber hyperplasia during the second half of gestation in Texel and Ujumqin sheep.
abstract: BACKGROUND
  Whether myofibers increase with a pulsed-wave mode at particular developmental stages or whether they augment evenly across developmental stages in large mammals is unclear. Additionally, the molecular mechanisms of myostatin in myofiber hyperplasia at the fetal stage in sheep remain unknown. Using the first specialized transcriptome-wide sheep oligo DNA microarray and histological methods, we investigated the gene expression profile and histological characteristics of developing fetal ovine longissimus muscle in Texel sheep (high muscle and low fat), as a myostatin model of natural mutation, and Ujumqin sheep (low muscle and high fat). Fetal skeletal muscles were sampled at 70, 85, 100, 120, and 135 d of gestation.
  
  
  RESULTS
  Myofiber number increased sharply with a pulsed-wave mode at certain developmental stages but was not augmented evenly across developmental stages in fetal sheep. The surges in myofiber hyperplasia occurred at 85 and 120 d in Texel sheep, whereas a unique proliferative surge appeared at 100 d in Ujumqin sheep. Analysis of the microarray demonstrated that immune and hematological systems' development and function, lipid metabolism, and cell communication were the biological functions that were most differentially expressed between Texel and Ujumqin sheep during muscle development. Pathways associated with myogenesis and the proliferation of myoblasts, such as calcium signaling, chemokine (C-X-C motif) receptor 4 signaling, and vascular endothelial growth factor signaling, were affected significantly at specific fetal stages, which underpinned fetal myofiber hyperplasia and postnatal muscle hypertrophy. Moreover, we identified some differentially expressed genes between the two breeds that could be potential myostatin targets for further investigation.
  
  
  CONCLUSIONS
  Proliferation of myofibers proceeded in a pulsed-wave mode at particular fetal stages in the sheep. The myostatin mutation changed the gene expression pattern in skeletal muscle at a transcriptome-wide level, resulting in variation in myofiber phenotype between Texel and Ujumqin sheep during the second half of gestation. Our findings provide a novel and dynamic description of the effect of myostatin on skeletal muscle development, which contributes to understanding the biology of muscle development in large mammals.
authors.affiliation: National Center for Molecular Genetics and Breeding of Animal, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China.
authors.forename: Hangxing
authors.initials: H
authors.lastname: Ren
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Hongwei
authors.initials: H
authors.lastname: Su
authors.forename: Lingyang
authors.initials: L
authors.lastname: Xu
authors.forename: Caihong
authors.initials: C
authors.lastname: Wei
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Hongbin
authors.initials: H
authors.lastname: Li
authors.forename: Wenzhong
authors.initials: W
authors.lastname: Liu
authors.forename: Lixin
authors.initials: L
authors.lastname: Du
mesh_terms: D000818:Animals; D002417:Cattle; D005260:Female; D005333:Fetus / Q000378:metabolism* / Q000473:pathology*; D020869:Gene Expression Profiling; D006801:Humans; D006965:Hyperplasia / Q000235:genetics / Q000473:pathology; D018485:Muscle Fibers, Skeletal / Q000378:metabolism* / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D015203:Reproducibility of Results; D012756:Sheep / Q000196:embryology* / Q000235:genetics; D013045:Species Specificity