Background: Spermatozoa in mammals develop in seminiferous tubules in a testis and are transported through the male reproductive tract. Their developmental origins are, however, different from each other; the seminiferous tubules are testicular (gonadal) structure but the subsequent ducts stem from the mesonephros. Although some mechanisms should function for the connection between these ducts, there are few reports on them. In the present study, basic information such as timing, localization, and cell types involved in the connection was obtained by sequential immunohistochemistry. Results: At the time when the undifferentiated gonad differentiates into the testis or ovary, Adrenal-4 binding protein/steroidogenic factor-1 (Ad4BP/SF-1)-positive gonadal cells were noted in the mesonephric tubules (MT) in both sexes. At an earlier stage, although Ad4BP/SF-1-positive coelomic epithelial cells were adjacent to the MT, a basal membrane around them was not observed. Conclusions:The connection between the testis cords and MT is suggested to be induced between Ad4BP/SF-1-positive gonadal cells and the MT before sex differentiation in a sex-independent manner. K E Y W O R D S efferent duct, male reproductive tract, sequential immunohistochemistry, testis development

Busulfan is an anti-cancer chemotherapeutic drug and is often used as conditioning regimens prior to bone marrow transplant for treatment of chronic myelogenous leukemia. Male infertility, including spermatogenesis disturbance, is known to be one of the side effects of anticancer drugs. While hormone preparations and vitamin preparations are used for spermatogenesis disturbance, their therapeutic effects are low. Some traditional herbal medicines have been administered to improve spermatogenesis. In the present study, we administered Gosha-jinki-gan (TJ107; Tsumura Co., Ltd., Tokyo, Japan) to mice suffering from severe aspermatogenesis after busulfan treatment to determine whether TJ107 can recover spermatogenesis. Male 4-week-old C57BL/6J mice were administered a single intraperitoneal injection of busulfan, and they were then fed a normal diet for 60 days and then a TJ107 diet or TJ107-free normal diet for another 60 days. After busulfan treatment, the weight of the testes and the epididymal sperm count progressively decreased in the normal diet group. On the other hand, in the TJ107 group, these variables dramatically recovered at 120 days. These results suggest that busulfan-induced aspermatogenesis is irreversible if appropriate treatment is not administered. Supplementation of TJ107 can completely recover the injured seminiferous epithelium via normalization of the macrophage migration and reduction of the expressions of Tool-like receptor (TLR) 2 and TLR4, suggesting that TJ107 has a therapeutic effect on busulfan-induced aspermatogenesis.

BackgroundThe testis is specific in that it produces haploid germ cells of which autoantigens newly appear long after the neonatal immune tolerance. Under normal condition, these autoantigens are protected by the blood‐testis barrier formed by Sertoli cells. Thus, the testis is an immunologically privileged site where haploid cells are protected from autoimmune attack.MethodsThe immunological microenvironment in the testis was experimentally investigated using mice and rats.Main findingsNot only the blood‐testis barrier but also various immuno‐suppressive factors are involved in the immune‐privileged testis. Indeed, germ cells transplanted into the xenogeneic seminiferous tubules could proliferate and differentiate with no aid of artificial immunosuppression. On the other hand, autoimmune orchitis could be experimentally produced by various methods of immunization with syngeneic or xenogeneic germ cell antigens.ConclusionOur results indicate that the testis is immunologically privileged but also immunologically fragile organ. Therefore, the dual nature is critical for immunoregulation of testicular function.

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