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

Abstract

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.

Sertoli cells control peritubular myoid cell fate and support adult Leydig cell development in the prepubertal testis

“…It remains possible, nevertheless, that changes in ALC differentiation may have been affected by altered macrophage numbers. Previous studies have suggested that macrophages generally enhance LC function and development (Chen et al, 2002;Gaytan et al, 1994), although activation of macrophage invasion can have an inhibitory effect (Hales, 2002). In this case, it appears unlikely that the marked reduction in ALC development following SC ablation is caused by the transient increase in macrophage numbers for the following three reasons.…”

Key factors in the regulation of fetal and postnatal leydig cell development

“…Testicular macrophages play an integral role in the interstitial tissue of the rat testis and secrete a number of cytokines, some of which are mitogenic to Leydig cells (Gaytan et al, 1994;Hutson, 1994). Impaired macrophage function leads to delayed or absent Leydig cell development, as supported by a model in which macrophages were depleted from the neonatal testis.…”

Yolk-sac–derived macrophages regulate fetal testis vascularization and morphogenesis

“…In the postnatal and adult testis, macrophages make up a large portion of the interstitial compartment (20) and are important for Leydig cell development and steroidogenic function (21,22). However, macrophages have not been detected or functionally characterized during fetal testis morphogenesis.…”