Neonatal Androgenization Affects the Intrathymic T-Cell Maturation in Rats

Abstract

The thymus structure, expression of CD4/CD8/TCRαβ on thymocytes and thymocyte proliferative and apoptotic indexes were analyzed in sexually immature 30-day-old and in sexually mature 60-day-old female rats neonatally androgenized (NA) by subcutaneous injection of 500 µg testosterone propionate/day on days 1–3 and in their vehicle-administered counterparts. The treatment affected normal thymus development. Thus, at 30 days of age, there was a reduction in the thymus weight, reflecting a decrease in the main thymic compartments. However, at 60 days of age, thymus weight did not significantly differ from that in age-matched controls, since the cortical volume enlargement was followed by a proportional decrease in the medullary volume. In rats of both ages, the changes in thymic compartments most likely reflected alterations in the size of both lymphoid and nonlymphoid components. Furthermore, in NA rats, substantial changes in thymocyte phenotypic characteristics were registered, in spite of their age. In both groups of NA rats, a decrease in the relative proportion of the least mature CD4–8–TCRαβ– cells and in that of CD4+8– TCRαβ–/TCRαβ^low cells followed by an increase in the percentage of their successor CD4+8+TCRαβ–/TCRαβ^low cells was detected. In addition, in 30-day-old NA rats, the relative proportions of CD4+8+TCRαβ^high cells (just positively selected) and that of mature single positive (CD4+8– and CD4–8+) and CD4–8– double negative TCRαβ^high cells, were reduced, while in 60-day-old NA rats only the percentage of CD4+8+TCRαβ^high thymocytes was decreased. Thus, the study showed that the changes in the development of the hypothalamo-pituitary-gonadal axis induced by neonatal androgenization may affect the thymus development and intrathymic T-cell maturation.