Perturbation of spermatogenesis by androgen antagonists directly injected into seminiferous tubules of live mice.
Natural and artificial substances present in the environment can affect our health. Testicular toxicants in particular are troublesome, because they disturb gonadal function of males. Translocation of substances into the seminiferous epithelium where sperm production proceeds is restricted due to the blood-testis barrier, but this permeability barrier temporarily disappears under physiological and sub-physiological conditions. This means that any substance could enter the seminiferous epithelium and disturb sperm production. To reduce the risk posed by such toxins, it is important to accurately determine which substances possess the toxicity. However, existing assay systems are not satisfactory in terms of both accuracy and sensitivity. Here, we report the establishment of such a system. We injected the androgen antagonists, flutamide and vinclozolin, directly into seminiferous tubules of live mice, which had been treated with busulfan for a temporal arrest of spermatogenesis, and the testes were histologically examined to see the effect of the injected materials on spermatogenesis that was in the process of recovery. The injection of either substance brought about a severe impairment of spermatogenesis at an amount over a million times smaller than that used in the previous assay systems where animals are administered with test substances outside of the testis. In contrast, these androgen antagonists at the same doses showed lesser effects when intratubularly or intraperitoneally administered into mice that had not been pretreated with busulfan. We propose that the method adopted in this study is a novel assay system to identify potential testicular toxicants.
Nagaosa
Kaz
K
Graduate School of Natural Science and Technology and Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920-1192, Japan.
Kishimoto
Atsushi
A
Kizu
Ryoichi
R
Nakagawa
Akihisa
A
Shiratsuchi
Akiko
A
Nakanishi
Yoshinobu
Y
D000726:Androgen Antagonists / Q000633:toxicity*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001814:Blood-Testis Barrier; D002066:Busulfan / Q000494:pharmacology; D005485:Flutamide / Q000633:toxicity*; D008297:Male; D051379:Mice; D008845:Microinjections; D010080:Oxazoles / Q000633:toxicity*; D012671:Seminiferous Tubules / Q000187:drug effects*; D013091:Spermatogenesis / Q000187:drug effects*; D018675:Toxicity Tests
D000726:Androgen Antagonists; D000970:Antineoplastic Agents; D010080:Oxazoles; D005485:Flutamide; D002066:Busulfan; C025643:vinclozolin