The purpose of this study was to investigate whether exposure of male mice to cisplatin induces apoptosis in male germ cells and the possible role of apoptosis in cisplatin-induced testicular damage. Forty-eight male BALB/c mice were divided into cisplatin and control groups. The mice from the cisplatin group received a single intraperitoneal injection of cisplatin of either 1, 5, or 10 mg/kg. The control group received a single intraperitoneal injection of saline alone. The testes were removed on days 1, 3, and 7 after cisplatin administration, respectively. Following histological examination, apoptotic indices (AIs) were measured within seminiferous tubules of the mouse testes by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay. A low incidence of spontaneous apoptosis was observed in controls, particularly in spermatogonia and spermatocytes of the mouse testes. After cisplatin administration, both increased Als and decreased spermatozoa and spermatids were found in the seminiferous tubules of the mouse testes. Cisplatin-induced apoptosis was found in spermatogonia, spermatocytes, and spermatids of the mouse testes. In comparison to the control values, AIs increased 2.6- to 6.8-fold in cisplatin-treated mouse testes. AIs reached the highest level on day 1 following 1 mg/ kg, on day 3 following 5 mg/kg, and on day 7 following treatment of 10 mg/kg cisplatin. The study showed that cisplatin-induced germ cell apoptosis in the mouse testes was related to both the dose response and the time course of response. It is suggested that cisplatin-induced germ cell apoptosis may result in decreased spermatogenesis, and the higher dose of cisplatin may delay the occurrence of apoptosis in the mouse testes.

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Our recent studies demonstrated that experimental autoimmune orchitis (EAO) model was produced in C3H/He mice with high incidence by two subcutaneous injections of viable syngeneic testicular germ cells (TC) without the use of any adjuvants or immunopotentiators. In this study the developmental patterns of autoantigenicity of TC during postnatal period were investigated by examining the orchitogenic activity of TC, the lymphostimulatory activities of TC (including the TC-induced in vitro lymphocyte proliferative response and the cytokine release from sensitized spleen cells (SPC) in response to TC) and the immunohistochemical localization of target autoantigens in the testes of mice at various weeks of age. Delayed-type hypersensitivity-inducing capacity and anti-TC antibody-eliciting capacity were initially observed in mice that were immunized with TC of 4-week old (w.o.) mice. The TC from 6-w.o. mice had the capability of inducing EAO (orchitogenicity) for the first time. A significant stimulation of in vitro lymphocyte proliferative response, as well as of interleukin (IL) 5 and IL-6 production by sensitized SPC were detectable when TC of mice 3-w.o. or more than were employed as stimulant. IL-2 and interferon gamma production were detected with TC of 4-w.o. mice. Immunohistochemical staining reaction with anti-TC antisera was primarily localized at the acrosomal portion of spermatids and spermatozoa in the seminiferous tubules, being already detected in spermatids of as early as 3-w.o. mice. Thus, from these data it is suggested that the appearance of the lymphostimulatory activities of TC consistently precedes that of the orchitogenic activity and that relatively mature germ cells such as spermatids and spermatozoa developing in the testes during the postnatal weeks may be responsible for the induction of disease and relevant immune responses in our EAO system.