Acute Copper Toxicity Displays a Nonmonotonic Relationship with Age Across the Medaka (Oryzias latipes) Life Span.

The ability of an organism to cope with environmental stressors varies across the life span because of developmental stage-specific responses and age-related functional declines. In the present study, we examined the effect of age on acute copper toxicity in Japanese medaka (Oryzias latipes). We first determined the median lethal concentration (LC50) at 96 h for embryos, 7-day-old fry, and 6-month-old medaka. Embryos were exposed to 0, 15, 30, 60, 125, 250, and 500 ppb CuSO4 through hatching. Fry were exposed to 0, 20, 50, 75, 100, 150, 250, and 500 ppb CuSO4 for 96 h. Adult fish were exposed to 0, 100, 150, 200, 250, and 300 ppb CuSO4 for 96 h. The 96-h LC50 was 804 ppb for embryos, 262 ppb for embryonically exposed larvae, 60.3 ppb for 7-day-old fry, and 226 ppb for adults. We then challenged cohorts of fish aged 2, 3, 5, 6, 7, 8, 9, 10, 11, 13, 14, 15, and 16 months with a 225-ppb CuSO4 exposure to determine the acute toxicity across the life span. The fish exhibited a bimodal tolerance to copper, with tolerance peaking in 2- and 3-month-old fish and again at 10 and 11 months of age. Our data demonstrate that copper sensitivity is dynamic throughout the medaka life span and may be influenced by trade-offs with reproduction. Environ Toxicol Chem 2022;41:2999-3006. © 2022 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Transient Copper Exposure During Embryogenesis and Temperature Affect Developmental Rate, Survival, and Fin Regeneration in Japanese Medaka (Oryzias latipes).

Combined environmental stressors that an organism experiences can have both immediate and lasting consequences. In the present study, we exposed Japanese medaka (Oryzias latipes) embryos to sublethal copper sulfate (CuSO4 ; 0, 10, and 100 ppb) in combination with different rearing temperatures (27, 30, and 33 °C) to assess acute and latent effects on development, growth, and regenerative capacity. Embryos exposed to CuSO4 and/or higher temperatures hatched significantly earlier. At 4 months post-exposure, fish exposed to low levels of CuSO4 during development had higher survival, whereas fish exposed to both 100 ppb CuSO4 and 33 °C temperatures had significantly lower survival. In addition, a sex-specific effect of embryonic CuSO4 exposure was observed as female mass decreased with increasing Cu dose. We also assessed caudal fin regenerative capabilities in both embryo-exposed fish at 4 months of age and adult medaka that were exposed to 0, 10, and 100 ppb CuSO4 at room temperature during a 14-day trial. Whereas fin regeneration was unaffected by adult exposure to Cu, fish transiently exposed during embryogenesis displayed an initial increase in fin growth rate and an increased incidence of abnormal fin morphology following regrowth. Collectively, these data suggest that developmental Cu exposure has the potential to exert long-lasting impacts to organismal growth, survival, and function. Environ Toxicol Chem 2022;41:748-757. © 2021 SETAC.

Exposure to ionizing radiation disrupts normal epigenetic aging in Japanese medaka.

Alterations to the epigenome are a hallmark of biological aging and age-dependent patterning of the DNA methylome ("epigenetic aging") can be modeled to produce epigenetic age predictors. Rates of epigenetic aging vary amongst individuals and correlate to the onset of age-related disease and all-cause mortality. Yet, the origins of epigenetic-to-chronological age discordance are not empirically resolved. Here, we investigate the relationship between aging, DNA methylation, and environmental exposures in Japanese medaka (Oryzias latipes). We find age-associated DNA methylation patterning enriched in genomic regions of low CpG density and that, similar to mammals, most age-related changes occur during early life. We construct an epigenetic clock capable of predicting chronological age with a mean error of 61.1 days (~8.4% of average lifespan). To test the role of environmental factors in driving epigenetic age variation, we exposed medaka to chronic, environmentally relevant doses of ionizing radiation. Because most organisms share an evolutionary history with ionizing radiation, we hypothesized that exposure would reveal fundamental insights into environment-by-epigenetic aging interactions. Radiation exposure disrupted epigenetic aging by accelerating and decelerating normal age-associated patterning and was most pronounced in cytosines that were moderately associated with age. These findings empirically demonstrate the role of DNA methylation in integrating environmental factors into aging trajectories.

Chronic low dose irradiation alters hepatic transcriptional profiles, but not global DNA methylation in medaka (Oryzias latipes).

Ionizing radiation (IR) resulting from both natural and anthropogenic sources is ubiquitous throughout the environment. Historically, studies on the biological impacts of radiation primarily focused on responses to acute doses of radiation, with little advancement in our understanding of environmentally relevant exposures. Epigenetic mechanisms are capable of mediating organismal responses to environmental stressors and DNA methylation plays important roles in gene regulation and promoting chromosomal stability. Here, we assess broad-scale transcriptional and epigenetic variation resulting from chronic exposure to low doses of ionizing radiation (LDIR; 5.78, 53.76, or 520.23 mGy/day) using Japanese medaka fish (Oryzias latipes) in a replicated mesocosm design. We observed significant changes to the hepatic transcriptome induced by a 3-month chronic exposure to IR, whereas global DNA methylation appeared largely unaffected. Our findings reveal a set of genes, including those involved in immune function, responding to environmentally relevant IR exposures, which do not appear to be mediated by a systemic global shift in DNA methylation.