EFFECTS OF MACROPHAGE DEPLETION AT DIFFERENT TIMES AFTER TREATMENT WITH ETHYLENE DIMETHANE SULFONATE (EDS) ON THE REGENERATION OF LEYDIG-CELLS IN THE ADULT-RAT

Testicular macrophages were selectively depleted in the right testes o f adult rats by an intratesticular injection of dichloromethylene diph osphonate-containing liposomes (Cl(2)MDP-lp), whereas the left testes were injected with 0.9% NaCl and served as control. Before or after Le ydig cell destruction with ethylene dimethane sulfonate (EDS), treatme nt with Cl(2)MDP-lp/NaCl was given at different times to study the req uirements of macrophages in the different stages of Leydig cell regene ration. On day 30 after EDS treatment, new Leydig cells were abundant in the left, macrophage-containing testes. However, in the right, macr ophage-depleted testes, the number of Leydig cells was related to the time elapsed between EDS treatment and macrophage depletion. When macr ophages were depleted on day 10 before or on days 4 or 10 after EDS tr eatment, new Leydig cells were nearly absent at 30 days. However, when macrophages were depleted on days 16 or 22 after EDS treatment, Leydi g cells were found at 30 days, but their numbers were equivalent to th e number of Leydig cells that were already present in EDS-treated anim als at the time the macrophages were depleted. These results indicate that macrophages are needed for the differentiation of Leydig cells fr om mesenchymal precursors, as well as for the proliferative activity o f the newly formed Leydig cells, possibly through the secretion of ess ential growth factors.