title: Effects of Intrauterine Growth Restriction During Late Pregnancy on the Development of the Ovine Fetal Thymus and the T-Lymphocyte Subpopulation.
abstract: OBJECTIVE
  The retarded development of fetal thymus in intrauterine growth restriction (IUGR) from maternal undernutrition during late pregnancy destroys the tridimensional structure and modifies the development of fetal T lymphocytes. The mechanisms, however, remain unclear. The objective of this study was to investigate the effect of IUGR during late pregnancy on the development of the ovine fetal thymus and the T-lymphocyte subpopulation.
  
  
  METHODS
  Eighteen time-mated ewes with singleton fetuses were allocated to three groups at day 90 of pregnancy: restricted group 1 (RG1, 0.18 MJ ME/BW(0.75) /day, n = 6), restricted group 2 (RG2, 0.33 MJ ME/BW(0.75) /day, n = 6) and a control group (CG, ad libitum, 0.67 MJ ME/BW(0.75) /day, n = 6). Fetuses were recovered at slaughter on day 140.
  
  
  RESULTS
  Fetuses in RG1 exhibited decreased (P < 0.05) thymic weight, cortical thickness, cortical:medullary, DNA content, total antioxidant capacity, and superoxide dismutase; intermediate changes were found in RG2 fetuses, including decreased thymic weight, cortical thickness, and DNA content (P < 0.05). The reductions (P < 0.05) of CD4(+) CD8(+) T cells, relative mRNA expression of keratin 8, recombination activating gene 1 (RAG1), and B-cell lymphoma 2 (Bcl-2) were found in both restricted groups. In addition, there was reduced mRNA expression (P < 0.05) of T-cell receptor, apoptosis antigen 1 ligand, and RAG2 in the RG1 group. In contrast, increases in glutathione peroxidase, malondialdehyde, caspase-3, Cytochrome c, and CD4(+) T cells were observed (P < 0.05), and higher mRNA expressions (P < 0.05) of protein 53, Bcl-2 associated X protein (Bax), and apoptosis antigen 1 (Fas) were found in RG1 fetuses; and thymuses of RG2 fetuses had increased caspase-3, and expression of Fas and Bax (P < 0.05), relative to control fetuses.
  
  
  CONCLUSIONS
  These results indicate that reduced cell proliferation, oxidative stress, and increased cell apoptosis were the potential mechanisms for impaired development and microenvironment of IUGR fetal thymus, and for modifying the maturation of CD4(+) CD8(+) thymocytes underlying their reduced numbers .
authors.affiliation: College of Life Science, Inner Mongolia Agricultural University, Hohhot, China.|Inner Mongolia Key Laboratory of Biomanufacturing, Hohhot, China.
authors.forename: Yingchun
authors.initials: Y
authors.lastname: Liu
authors.affiliation: College of Animal Science, Inner Mongolia Agricultural University, Hohhot, China.
authors.forename: Shan
authors.initials: S
authors.lastname: He
authors.affiliation: College of Animal Science, Inner Mongolia Agricultural University, Hohhot, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: College of Life Science, Inner Mongolia Agricultural University, Hohhot, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xia
authors.affiliation: College of Animal Science, Inner Mongolia Agricultural University, Hohhot, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.affiliation: College of Animal Science, Inner Mongolia Agricultural University, Hohhot, China.
authors.forename: Chongzhi
authors.initials: C
authors.lastname: Zhang
authors.affiliation: College of Animal Science, Inner Mongolia Agricultural University, Hohhot, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology; D053148:Caspase 3 / Q000096:biosynthesis; D053181:Caspase 8 / Q000096:biosynthesis; D053453:Caspase 9 / Q000096:biosynthesis; D049109:Cell Proliferation; D045304:Cytochromes c / Q000096:biosynthesis; D005260:Female; D047109:Fetal Development; D005317:Fetal Growth Retardation / Q000276:immunology*; D005333:Fetus / Q000196:embryology; D044342:Malnutrition / Q000503:physiopathology*; D008969:Molecular Sequence Data; D018384:Oxidative Stress / Q000276:immunology; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D011248:Pregnancy Complications / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis; D012756:Sheep; D016176:T-Lymphocyte Subsets / Q000166:cytology*; D013950:Thymus Gland / Q000196:embryology*
chemical_list: D011948:Receptors, Antigen, T-Cell; D045304:Cytochromes c; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9
keywords: Development; T-lymphocyte subsets; fetal growth restriction; maternal undernutrition; ovine fetal thymus