Mechanistic insight into the reprotoxic effects of chronic gamma radiation on spermatogenesis in Caenorhabditis elegans

Ionizing radiation is a potent genotoxic agent that may cause detrimental effects on reproductive processes. This study investigated cellular events and transcriptomic alterations underlying reproductive defects caused by chronic gamma (γ) radiation in Caenorhabditis elegans (C. elegans). Continuous exposure (100 mGy/h; total dose: 4.8 Gy) throughout larval development reduced spermatid counts (38.8%) and total brood size (26.4%). It also resulted in delayed and attenuated residual body (RB) formation (22.8%), implicating reduced number of spermatocytes or failed meiosis. Targeted exposure of early L3 to L4 (24-h, total dose 2.4 Gy) after the establishment of the primary spermatocyte population resulted in 26% reduction in brood size, thus implicating damage inflicted during meiosis as detrimental to spermatogenesis. The reprotoxic defects were markedly exacerbated by rad-51 RNAi or polq-1 deletion, confirming the crucial roles for homologous recombination (HR) and polymerase theta-mediated end joining (TMEJ) in mitigating radiation-induced reproductive damage. Phenotypical investigation of the male gonad revealed genotoxic effects including shortened mitotic zone and increased cell-cycle arrest. However, the postmeiotic stage assessed as the quantity of RB-containing phagosomes remained unaffected by ionizing radiation. Transcriptomic profiling of irradiated males showed comprehensive enhanced stress response and mitophagy accompanied by alterations of energy metabolism. Comparative transcriptomic analysis revealed large differences between sexes, where the only shared enrichment term was mitochondrial translation termination. Collectively, our results show that detrimental effects to hermaphrodite spermatogenesis occur during the meiotic phase, which leads to fewer RBs and spermatids, with a corresponding reduction in reproduction.