Neonatal testosterone imprinting affects thymus development and leads to phenotypic rejuvenation and masculinization of the peripheral blood T-cell compartment in adult female rats

  • Leposavić G
  • Perišić M
  • Kosec D
 et al. 
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Exposure of female rodents to testosterone in the critical neonatal period produces defeminization/masculinization of the hypothalamo-pituitary-gonadal (HPG) axis, i.e. neonatal androgenization and postpones axis maturation. To address the hypothesis that HPG axis signaling is involved in the programming of thymic maturation/involution and sexual differentiation we studied the impact of neonatal androgenization on thymic cellularity, development of effector and regulatory T cells, and phenotypic characteristics of peripheral blood T lymphocytes in adult rats. A single injection of testosterone on postnatal day 2 postponed thymic maturation/involution as revealed by organ hypercellularity, increased cellularity of the most mature (CD4+CD8- and CD4-CD8+) TCRαβhighthymocyte and both recent thymic emigrant (RTE) subsets and caused phenotypic defeminization/masculinization of thymic (decreased CD4+CD8-TCRαβhigh/CD4-CD8+TCRαβhig hcell ratio) and peripheral blood T-cell compartments (decreased CD4+RTE/CD8+RTE and CD4+/CD8+ cell ratio). In addition, neonatal androgenization increased the relative and absolute numbers of both CD4+CD25+Foxp3+ and natural killer (NK) regulatory T cells in peripheral blood. These findings, in conjunction with thymocyte overexpression of Thy-1 that is assumed to reduce negative selection affecting self-reactive cell generation, suggest a new relationship between self-reactive and regulatory T cells. In conclusion, our study provides additional evidence for a role of HPG signals (i.e. sex steroids and gonadotropins) in programming the kinetics of thymic maturation/involution and in establishing immunological sexual dimorphism. © 2008 Elsevier Inc. All rights reserved.

Author-supplied keywords

  • Neonatal androgenization
  • Peripheral blood T lymphocytes
  • Recent thymic emigrants
  • T-cell differentiation

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  • Gordana Leposavić

  • Milica Perišić

  • Duško Kosec

  • Nevena Arsenović-Ranin

  • Katarina Radojević

  • Zorica Stojić-Vukanić

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