본문 바로가기
KERD
논문KCI 등재

Effects of intrauterine growth restriction during late pregnancy on the cell growth, proliferation, and differentiation in ovine fetal thymuses

He Shan|Zhang Min|Gao Feng|Zi Yang|Ma Chi|Yang Huan|Liu Yingchun
아세아·태평양축산학회 (Asian-Australasian Association Of Animal Production Societies)|2022.07|Animal Bioscience|제35권 제7호|pp. 989-998|DOI 10.5713/ab.21.0414

1

조회

0

다운로드

0

인용

0

참고문헌

키워드

Cell Cycle ArrestCell DifferentiationMaternal UndernutritionOvine Fetal Thymus

초록

Objective: This study investigated the effects of intrauterine growth restriction (IUGR) during late pregnancy on the cell growth, proliferation, and differentiation in ovine fetal thymuses. Methods: Eighteen time-mated Mongolian ewes with singleton fetuses were allocated to three groups at d 90 of pregnancy: restricted group 1 (RG1, 0.18 MJ ME/body weight [BW]0.75/d, n = 6), restricted group 2 (RG2, 0.33 MJ ME/BW0.75/d, n = 6) and control group (CG, ad libitum, 0.67 MJ ME/BW0.75/d, n = 6). Fetuses were recovered at slaughter on d 140. Results: The G0/G1 phase cell number in fetal thymus of the RG1 group was increased but the proliferation index and the expression of proliferating cell nuclear antigen (PCNA) were reduced compared with the CG group (p<0.05). Fetuses in the RG1 group exhibited decreased growth hormone receptor (GHR), insulin-like growth factor 2 receptor (IGF-2R), and their mRNA expressions (p<0.05). For the RG2 fetuses, there were no differences in the proliferation index and PCNA expression (p>0.05), but growth hormone (GH) and the mRNA expression of GHR were lower than those of the CG group (p<0.05). The thymic mRNA expressions of cyclin-dependent protein kinases (CDKs including CDK1, CDK2, and CDK4), CCNE, E2-factors (E2F1, E2F2, and E2F5) were reduced in the RG1 and RG2 groups (p<0.05), and decreased mRNA expressions of E2F4, CCNA, CCNB, and CCND were occurred in the RG1 fetuses (p<0.05). The decreased E-cadherin (E-cad) as a marker for epithelial-mesenchymal transition (EMT) was found in the RG1 and RG2 groups (p<0.05), but the OB-cadherin which is a marker for activated fibroblasts was increased in fetal thymus of the RG1 group (p<0.05). Conclusion: These results indicate that weakened GH/IGF signaling system repressed the cell cycle progression in G0/G1 phase in IUGR fetal thymus, but the switch from reduced E-cad to increased OB-cadherin suggests that transdifferentiation process of EMT associated with fibrogenesis was strengthened. The impaired cell growth, retarded proliferation and modified differentiation were responsible for impaired maturation of IUGR fetal thymus.

Abstract

Objective: This study investigated the effects of intrauterine growth restriction (IUGR) during late pregnancy on the cell growth, proliferation, and differentiation in ovine fetal thymuses. Methods: Eighteen time-mated Mongolian ewes with singleton fetuses were allocated to three groups at d 90 of pregnancy: restricted group 1 (RG1, 0.18 MJ ME/body weight [BW]0.75/d, n = 6), restricted group 2 (RG2, 0.33 MJ ME/BW0.75/d, n = 6) and control group (CG, ad libitum, 0.67 MJ ME/BW0.75/d, n = 6). Fetuses were recovered at slaughter on d 140. Results: The G0/G1 phase cell number in fetal thymus of the RG1 group was increased but the proliferation index and the expression of proliferating cell nuclear antigen (PCNA) were reduced compared with the CG group (p<0.05). Fetuses in the RG1 group exhibited decreased growth hormone receptor (GHR), insulin-like growth factor 2 receptor (IGF-2R), and their mRNA expressions (p<0.05). For the RG2 fetuses, there were no differences in the proliferation index and PCNA expression (p>0.05), but growth hormone (GH) and the mRNA expression of GHR were lower than those of the CG group (p<0.05). The thymic mRNA expressions of cyclin-dependent protein kinases (CDKs including CDK1, CDK2, and CDK4), CCNE, E2-factors (E2F1, E2F2, and E2F5) were reduced in the RG1 and RG2 groups (p<0.05), and decreased mRNA expressions of E2F4, CCNA, CCNB, and CCND were occurred in the RG1 fetuses (p<0.05). The decreased E-cadherin (E-cad) as a marker for epithelial-mesenchymal transition (EMT) was found in the RG1 and RG2 groups (p<0.05), but the OB-cadherin which is a marker for activated fibroblasts was increased in fetal thymus of the RG1 group (p<0.05). Conclusion: These results indicate that weakened GH/IGF signaling system repressed the cell cycle progression in G0/G1 phase in IUGR fetal thymus, but the switch from reduced E-cad to increased OB-cadherin suggests that transdifferentiation process of EMT associated with fibrogenesis was strengthened. The impaired cell growth, retarded proliferation and modified differentiation were responsible for impaired maturation of IUGR fetal thymus.

참고문헌 (47)

  1. Savino W, "The thymus is a common target in malnutrition and infection", Br J Nutr, 98, pp.S11~S16 (2007)[DOI]
  2. Ortiz R, "Malnutrition alters the rates of apoptosis in splenocytes and thymocyte subpo pulations of rats", Clin Exp Immunol, 155, pp.96~106 (2009)[DOI]
  3. Manley NR, "Thymus organogenesis and molecular mechanisms of thymic epithelial cell differentiation", Semin Immunol, 12, pp.421~428 (2000)[DOI]
  4. Gao F, "Study of the effect of IUGR during late pregnancy on the immune capability of neonatal lambs", Prog Nat Sci China(chinese), 16, pp.1336~1340 (2006)
  5. Palmer AC, "Nutritionally mediated programming of the developing immune system", Adv Nutr, 2, pp.377~395 (2011)[DOI]
  6. Robinson JJ, "Nutritional effects on foetal growth", Anim Sci, 68, pp.315~331 (1999)[DOI]
  7. McMillen IC, "Fetal growth restriction : adaptations and consequences", Reproduction, 122, pp.195~204 (2001)[DOI]
  8. Osgerby JC, "The effect of maternal undernutrition on ovine fetal growth", J Endocrinol, 173, pp.131~141 (2002)[DOI]
  9. Greenwood PL, "Consequences of intra-uterine growth retardation for postnatal growth, metabolism and pathophysiology", Reprod Suppl, 61, pp.195~206 (2003)
  10. Cromi A, "Ultrasonographic measurement of thymus size in IUGR fetuses : a marker of the fetal immunoendocrine response to malnutrition", Ultrasound Obstet Gynecol, 33, pp.421~426 (2009)[DOI]
  11. Ekin A, "Prognostic value of fetal thymus size in intrauterine growth restriction", J Ultrasound Med, 35, pp.511~517 (2016)[DOI]
  12. Olearo E, "Thymic volume in healthy, small for gestational age and growth restricted fetuses", Prenat Diagn, 32, pp.662~667 (2012)[DOI]
  13. Contreras YM, "Intrauterine growth restriction alters T-lymphocyte cell number and dual specificity phosphatase 1 levels in the thymus of newborn and juvenile rats", Pediatr Res, 70, pp.123~129 (2011)[DOI]
  14. Liu Y, "Effects of intrauterine growth restriction during late pregnancy on the development of the ovine fetal thymus and the T-lymphocyte subpopulation", Am J Reprod Immunol, 74, pp.26~37 (2015)[DOI]
  15. Morrison JL, "Sheep models of intrauterine growth restriction : fetal adaptations and consequences", Clin Exp Pharmacol Physiol, 35, pp.730~743 (2008)[DOI]
  16. "The State Science and Technology Commission of China:Regulations for administration of affairs concerning experimental animal" (1988), The China Legal System Publishing House Press
  17. Symonds ME, "Fetal endocrinology and development-manipulation and adaptation to long-term nutritional and environmental challenges", Reproduction, 121, pp.853~862 (2001)[DOI]
  18. Gao F, "Effect of intrauterine growth restriction during late pregnancy on the growth performance, blood components, immunity and anti-oxidation capability of ovine fetus", Livest Sci, 155, pp.435~441 (2013)[DOI]
  19. Liu YC, "Effects of intrauterine growth restriction during late pregnancy on the cell apoptosis and related gene expression in ovine fetal liver", Theriogenology, 90, pp.204~209 (2017)[DOI]
  20. Sambrook J, "Molecular cloning: a laboratory manual" (2001), Cold Spring Harbor Laboratory Press
  21. Livak KJ, "Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method", Methods, 25, pp.402~408 (2001)[DOI]
  22. STAT user’s guide, "SAS", pp.2001, SAS Institute
  23. Bacon WA, "Single-cell analysis identifies thymic maturation delay in growth-restricted neonatal mice", Front Immunol, 9, pp.2523~ (2018)[DOI]
  24. Mitsumori K, "Morphometric and immunohistochemical studies on atrophic changes in lympho-hematopoietic organs of rats treated with piperonyl butoxide or subjected to dietary restriction", Arch Toxicol, 70, pp.809~814 (1996)[DOI]
  25. Urrego D, "Potassium channels in cell cycle and cell proliferation", Philos Trans R Soc Lond B Biol Sci, 369, pp.20130094~ (2014)[DOI]
  26. Hindley C, "The cell cycle and pluripotency", Biochem J, 451, pp.135~143 (2013)[DOI]
  27. Kalucka J, "Metabolic control of the cell cycle", Cell Cycle, 14, pp.3379~3388 (2015)[DOI]
  28. Massagué J, "G1 cell-cycle control and cancer", Nature, 432, pp.298~306 (2004)[DOI]
  29. Zonis S, "p21Cip restrains hippocampal neurogenesis and protects neuronal progenitors from apoptosis during acute systemic inflammation", Hippocampus, 23, pp.1383~1394 (2013)[DOI]
  30. Bretones G, "Myc and cell cycle control", Biochim Biophys Acta, 1849, pp.506~516 (2015)[DOI]
  31. Satyanarayana A, "Mammalian cell-cycle regulation : several Cdks, numerous cyclins and diverse compensatory mechanisms", Oncogene, 28, pp.2925~2939 (2009)[DOI]
  32. Kitagawa M, "Cell cycle regulation by long non-coding RNAs", Cell Mol Life Sci, 70, pp.4785~4794 (2013)[DOI]
  33. Lim SH, "Cdks, cyclins and CKIs: roles beyond cell cycle regulation", Development, 140, pp.3079~3093 (2013)[DOI]
  34. Wong JV, "Network calisthenics : control of E2F dynamics in cell cycle entry", Cell Cycle, 10, pp.3086~3094 (2011)[DOI]
  35. Jing J, "A feedback regulatory loop involving p53", miR-200 and growth hormone endocrine axis controls embryo size of zebrafish, 2015, pp.5, 15906~
  36. Savino W, "Neuroendocrine control of T cell development in mammals: role of growth hormone in modulating thymocyte migration", Exp Physiol, 92, pp.813~817 (2007)[DOI]
  37. Lins MP, "Growth hormone in the presence of laminin modulates interaction of human thymic epithelial cells and thymocytes in vitro", Biol Res, 49, pp.37~ (2016)[DOI]
  38. ChentoufiAA, "Thymic self-antigen expression for the design of a negative", tolerogenic self-vaccine against type 1 diabetes, 2011, pp.2011, 349368~
  39. Geenen V, "The thymic insulin-like growth factor axis : involvement in physiology and disease", Horm Metab Res, 35, pp.656~663 (2003)[DOI]
  40. Boguszewski CL, "Growth hormone, insulin-like growth factor system and carcinogenesis", Endokrynol Pol, 67, pp.414~426 (2016)[DOI]
  41. Hay ED, "Transformations between epithelium and mesenchyme : normal, pathological, and experimentally induced", Am J Kidney Dis, 26, pp.678~690 (1995)[DOI]
  42. Manley NR, "Structure and function of the thymic microenvironment", Front Biosci(Landmark Ed), 16, pp.2461~2477 (2011)[DOI]
  43. Sun L, "Thymic epithelial cell development and its dysfunction in human diseases", Biomed Res Int, 2014, pp.206929~ (2014)[DOI]
  44. Larue L, "Epithelial-mesenchymal transition in development and cancer : role of phosphatidylinositol 3′kinase", AKT pathways, 2005, pp.24, 7443~7454
  45. Thompson EW, "Carcinoma invasion and metastasis : a role for epithelial-mesenchymal transition?", Cancer Res, 65, pp.5991~5995 (2005)[DOI]
  46. Strutz F, "Role of basic fibroblast growth factor-2 in epithelial-mesenchymal transformation", Kidney Int, 61, pp.1714~1728 (2002)[DOI]
  47. Lamouille S, "Molecular mechanisms of epithelial-mesenchymal transition", Nat Rev Mol Cell Biol, 15, pp.178~196 (2014)[DOI]

이 간행물의 다른 논문 (15건)

Mitochondrial sequence based characterization and morphometric assessment of Diara buffalo populationSingh Ramesh Kumar, Purohit Hitesh, Singh Karan Veerpp. 949-954Genetic study of quantitative traits supports the use of Guzerá as dual-purpose cattleBruneli Frank Angelo Tomita, Zadra Lenira El Faro, Ventura Henrique Torres, Josahkian Luiz Antônio, Lopes Paulo Sávio, Silva Fabyano Fonseca e, Ramos Pedro Vital Brasil, Carrara Eula Regina, Peixoto Maria Gabriela Campolina Diniz, Veroneze Renatapp. 955-963The highly pathogenic H5N1 avian influenza virus induces the mitogen-activated protein kinase signaling pathway in the trachea of two Ri chicken lines부 티 하오, Lee Sooyeon, Lillehoj,Hyun S., Truong Anh Duc, 홍영호, Heo Jubi, Hong Yeojinpp. 964-974Long non-coding RNAs in Sus scrofa ileum under starvation stressLu Chang, Yang Yang, Zhao Yan, Wang Shu, Ma Yi Jia, Li Yong Shi, Ge Xu Sheng, Cai Chunbo, Liang Guo Ming, Guo Xiaohong, Cao Guoqing, Li Bugao, Gao Pengfeipp. 975-988Effects of rice straw fermented with spent Pleurotus sajor-caju mushroom substrates on milking performance in Alpine dairy goatsLee Tzu Tai, Lee Churng-Faung, Yu Bi, Chen Mei-Hsing, Fan Geng-Jenpp. 999-1009
원문 보기