Requirement for testicular macrophages in Leydig cell proliferation and differentiation during prepubertal development in rats.

Testicular macrophages in rats were selectively depleted by an intratesticular injection of liposomes containing dichloromethylene diphosphonate into the right testis to study the possible role of these macrophages during the prepubertal development of Leydig cells. The contralateral testes were injected with 0.9% NaCl and served as controls. The animals were injected with the liposomes and NaCl at 5, 10, 15, 20 or 25 days of age. In macrophage-depleted testes, Leydig cell development was inhibited in the animals injected at 5, 10 or 15 days of age. At 35 days of age, the testis was repopulated with macrophages and Leydig cells also developed. Rats treated at 20 or 25 days of age, when Leydig cells were already present in low numbers, did not show any further increases in the number of Leydig cells up to 35 days of age. To study whether the effects of gonadotrophins on Leydig cell development require the presence of macrophages, 21-day-old rats, injected 3 days before with liposomes (right testis) and NaCl (left testis), were treated with 75 iu human FSH kg-1 bodymass day-1, 10 iu hCG per rat day-1, combined hFSH and hCG, or vehicle (PBS with 0.5% BSA) for 6 days. Treatment with hCG induced a sevenfold increase in the number of Leydig cells in the left (macrophage-containing) testis, whereas no increase was found in the right (macrophage-depleted) testis. These results indicate that macrophages are needed for Leydig cell development and for the Leydig cell response to hCG during postnatal maturation.