Ionizing radiation is a well-known environmental stressor capable of generating excessive reactive oxygen species (ROS), leading to oxidative damage in sensitive tissues, including the reproductive system. While oxidative stress is increasingly implicated in male reproductive dysfunction, the long-term effects of low-dose-rate (LDR) radiation on testicular structure and oxidative status remain underexplored. In this study, mice were exposed to continuous LDR radiation (0.39, 1.29, and 3.46 mGy/h) for 21 days to assess testicular histopathology and oxidative status. Although testis weight did not significantly differ among groups, histological analysis revealed basal membrane disruption and reduced spermatogenic cell populations in irradiated groups. Masson’s Trichrome and Sirius Red staining demonstrated dose-dependent collagen deposition, indicating progressive testicular fibrosis. TUNEL assays confirmed increased germ cell apoptosis in the mid- and high-dose-rate groups. ROS levels were significantly elevated only in the highest-dose group, suggesting a threshold-dependent oxidative stress response. These findings indicate that chronic LDR radiation induces testicular damage primarily through apoptosis and fibrosis, with oxidative stress potentially contributing at higher exposure levels.

Min Seok Woo, Eun-Jin Kim, Anjas Happy Prayoga, Yangmi Kim and Dawon Kang. Journal of Animal Reproduction and Biotechnology 2023;38:291-9. https://doi.org/10.12750/JARB.38.4.291

Our previous study highlighted the anticancer potential of sea hare hydrolysate (SHH), particularly its role in regulating macrophage polarization and inducing pyroptotic death in lung cancer cells through the inhibition of signal transducer and activator of transcription 3 (STAT3). These findings prompted us to investigate additional features of immune‐oncology (I‐O) agents or adjuvants, such as programmed cell death protein 1 (PD‐1)/programmed death ligand 1 (PD‐L1) inhibition and their association with rheumatoid arthritis (RA) risk, to explore the potential of SHH as an I‐O agent or adjuvant. In this study, we investigated the effects of SHH on PD‐L1 levels in various cancer cell types and assessed its effectiveness in treating RA, a common side effect of I‐O agents. Our results showed a marked reduction in PD‐L1 levels in multiple cancer cell lines and decreased PD‐1 and PD‐L1 levels in tumor‐associated macrophages. In a mouse model with collagen‐induced arthritis (CIA), SHH exhibited anti‐inflammatory effects comparable to methotrexate (MTX), a first‐line treatment for RA. Both the SHH and MTX groups had significantly lower arthritis scores and paw thickness compared to the CIA group. Additionally, SHH or MTX treatment effectively reduced elevated levels of anticollagen type II (CII) antibodies and proinflammatory cytokines (IL‐1β, IL‐6, and TNF‐α). Histopathological analysis revealed that SHH and MTX treatments notably mitigated arthritic inflammation, synovial hyperplasia, and loss of articular cartilage and bone. Micro‐CT scans showed reduced articular destruction in the SHH and MTX groups. These findings indicate that SHH treatment decreases PD‐L1 levels in cancer cells and reduces the severity of CIA by exerting anti‐inflammatory effects. Therefore, SHH holds promise as an I‐O agent without side effects such as exacerbation of RA.

Ionizing radiation is a potent environmental stressor capable of generating excessive reactive oxygen species (ROS), leading to oxidative damage in various tissues, including reproductive organs. Despite growing awareness of oxidative stress in reproductive failure, the long-term effects of low-dose-rate (LDR) radiation on testicular function and redox imbalance remain underexplored. This study investigated the effect of prolonged LDR radiation exposure (0.39, 1.29, and 3.46 mGy/h) on mice's testicular histology and oxidative status. Although no significant differences in testis weight were observed, histological analysis revealed basal membrane disruption and reduced spermatogenic cell populations in irradiated groups. Masson's Trichrome and Sirius Red staining demonstrated dose-dependent collagen accumulation, indicating progressive testicular fibrosis. TUNEL assays confirmed increased germ cell apoptosis, while oxidative stress levels were significantly increased in the highest dose group (3.46 mGy/h). Our findings suggest that chronic LDR radiation induces testicular injury through ROS overproduction, triggering apoptosis and extracellular matrix remodeling.