Animal Bioscience (Jul 2022)

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

  • Yang Zi,
  • Chi Ma,
  • Shan He,
  • Huan Yang,
  • Min Zhang,
  • Feng Gao,
  • Yingchun Liu

DOI
https://doi.org/10.5713/ab.21.0414
Journal volume & issue
Vol. 35, no. 7
pp. 989 – 998

Abstract

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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 (p0.05), 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.

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