Local Regulation of Macrophage Subsets in the Adult Rat Testis: Examination of the Roles of the Seminiferous Tubules, Testosterone, and Macrophage-Migration Inhibitory Factor1

Abstract

In the adult rat testis, macrophages belong to one of two subsets differentiated by expression or lack of expression of the resident macrophage surface antigen recognized by monoclonal antibody ED2. Local regulation of the testicular macrophage subsets was investigated in normal and 4-wk experimentally cryptorchid adult rats with and without s.c. testosterone implants (T-implants). Macrophage subsets ED2(+) (resident-type) and ED2(-) (monocyte-like) were identified immunohistochemically and counted in perfusion-fixed frozen testis sections. Depletion of the spermatogenic cells by cryptorchidism had no effect on testicular macrophage numbers. Inhibition of Leydig cell and seminiferous tubule function by low-dose (3 cm) T-implants caused a 40% reduction in ED2(+) resident macrophages in both scrotal and abdominal testes. High-dose (24 cm) T-implants, which inhibit Leydig cell function while maintaining normal seminiferous tubule function, also reduced the number of resident macrophages by approximately 40%, although this reduction was at least partially prevented in the abdominal testes. In the scrotal testis only, the ED2(-) monocyte/macrophage subset was significantly reduced in number by low-dose, but not high-dose, T-implants. The concentration of the Leydig cell-secreted cytokine macrophage-migration inhibitory factor (MIF) in testicular fluid was reduced by cryptorchidism, but not by the T-implants. When data from all experimental groups were combined, ED2(+) resident macrophage numbers showed a significant positive correlation with parameters of Leydig cell function (serum LH and testicular testosterone levels) but a negative correlation with MIF levels. This study indicates that Leydig cells regulate testicular macrophage numbers directly, rather than via an effect upon the seminiferous epithelium, in the adult rat testis. The data also suggest that testosterone and MIF play only a minor role, if any, in this regulation.

Testosterone Replacement Effectively Inhibits the Development of Experimental Autoimmune Orchitis in Rats: Evidence for a Direct Role of Testosterone on Regulatory T Cell Expansion

“…In our study, the administration of T3 implant as expected resulted in the reduction of serum gonadotropin levels below those necessary to sustain spermatogenesis. In contrast, the higher-dose T24 implants cause supraphysiological serum concentrations and resulted in sufficient levels (10-40% of normal testicular levels) to support qualitatively normal seminiferous tubule function (40,45,46). The histological assessment of the treated animals clearly showed that testosterone replacement provided a significant degree of protection against the development of orchitis with only 17% of EAO+T3 and 33% of EAO+ T24 animals developing the disease, compared with 80% when no hormone intervention was performed.…”

Professional phagocytic granulocytes of the bony fish gilthead seabream display functional adaptation to testicular microenvironment

“…Thus, mammalian testicular macrophages display a novel cytokine secretion profile compared with peritoneal macrophages [24] and retain their cytotoxic and phagocytic capacities, although they have greatly diminished proinflammatory functions and exhibit immunosuppressive activity [25]. Moreover, the recruitment and maintenance of the resident macrophages are clearly under the control of testicular soluble factors [26], such as macrophage migration inhibitory factor [27] and monocyte chemoattractant protein-1 [28,29]. The testicular sbNLCs are also recruited by testicular soluble factors, show a different cytokine production profile [8], and retain some phagocytic and ROI production capabilities, although they are impaired severely by the testicular microenvironment.…”

Cytokine profiles in the testes of rats treated with lipopolysaccharide reveal localized suppression of inflammatory responses

“…Testicular IF was assayed for testosterone without extraction using a direct 125 I-testosterone radioimmunoassay (44).…”