Heavy-Ion-Induced Gonocyte Apoptosis and Its Modification in Cultured Fetal Rat Testes

The ground-based experiments using accelerated heavy ions are of critical importance for studying the biological effects from high-LET ionizing radiation concerning the human activities in space missions. We reported previously that heavy-ion irradiations on E15 generally induced markedly detrimental effects on prenatal gonads, postnatal testicular development and male breeding activity in Wistar rats. To explore the mechanisms underlying radiation-induced gonocyte apoptosis in fetal gonads, which played a vital role in the fate of postnatal testis development, carbon and neon-ion irradiations of cultured fetal rat testes were applied to investigations focused on cellular and molecular events with or without inhibitors of p53, gap junction, or pan-caspase, or nitric oxide specific scavenger. Results showed that, in addition to the clustered distribution, the time course and the percentage of apoptosis on E15 equivalent in vitro appeared similar to that in utero. Carbon-ion irradiations induced increased p53 expression and decreased expressions of p21 and Bcl-2 in a dose dependent manner. Pan-caspase inhibitor effectively inhibited apoptosis occurrence and reduced the extent of clustered distribution, while such effects were not observed with the presence of p53 or gap junction inhibitor, or nitric oxide specific scavenger. These findings indicated that irradiations of cultured fetal testes manifested pathologically similar gonocyte apoptosis to that in utero. The apoptosis was independent on p53, gap junction and nitric oxide. p53 expression was possibly responsible for the response to radiation damage rather than induction of apoptosis. The syncytial organization of gonocytes played a key role in formation of the clustered apoptosis.