Gamma irradiation during gametogenesis in young adult zebrafish causes persistent genotoxicity and adverse reproductive effects

Abstract

The biological effects of gamma radiation may exert damage beyond that of the individual through its deleterious effects on reproductive function. Impaired reproductive performance can result in reduced population size over consecutive generations. In a continued effort to investigate reproductive and heritable effects of ionizing radiation, we recently demonstrated adverse effects and genomic instability in progeny of parents exposed to gamma radiation. In the present study, genotoxicity and effects on the reproduction following subchronic exposure during a gametogenesis cycle to Co gamma radiation (27 days, 8.7 and 53 mGy/h, total doses 5.2 and 31 Gy) were investigated in the adult wild-type zebrafish (Danio rerio). A significant reduction in embryo production was observed one month after exposure in the 53 mGy/h exposure group compared to control and 8.7 mGy/h. One year later, embryo production was significantly lower in the 53 mGy/h group compared only to control, with observed sterility, accompanied by a regression of reproductive organs in 100% of the fish 1.5 years after exposure. Histopathological examinations revealed no significant changes in the testis in the 8.7 mGy/h group, while in 62.5% of females exposed to this dose rate the oogenesis was found to be only at the early previtellogenic stage. The DNA damage determined in whole blood, 1.5 years after irradiation, using a high throughput Comet assay, was significantly higher in the exposed groups (1.2 and 3-fold increase in 8.7 and 53 mGy/h females respectively; 3-fold and 2-fold increase in 8.7 and 53 mGy/h males respectively) compared to controls. A significantly higher number of micronuclei (4-5%) was found in erythrocytes of both the 8.7 and 53 mGy/h fish compared to controls. This study shows that gamma radiation at a dose rate of ≥ 8.7 mGy/h during gametogenesis causes adverse reproductive effects and persistent genotoxicity (DNA damage and increased micronuclei) in adult zebrafish.

Ionizing radiation induces transgenerational effects of DNA methylation in zebrafish

“…The dose compares to observations from Chernobyl, where the total accumulated dose over 60 days post-accident was estimated at 10 Gy 49 . These doses did not cause effects on survival in our study on directly exposed adult zebrafish 50 . The swimming space volume was approximately 6 L (16 × 18 × 22 cm) with custom made grids.…”

“…Other overrepresented pathways following gene expression as well as DNA methylation analysis could indicate effects that manifest later in life, such as axonal guidance signalling involved in neurodevelopment, and FSH signalling linked to reproductive outcome. Interestingly, irradiated parents exhibited effects on ovaries with an increase in pre-vitellogenic follicles, indicating effects on maturation of oocytes, which could involve FSH signalling 50 . These results indicate potential novel affected molecular mechanisms in radiation response.…”

The comet assay in animal models: From bugs to whales – (Part 2 Vertebrates)

“…Apart from using zebrafish as an in vivo model system, in addition to the zebrafish embryo model that can be regarded as an in vitro method, the use of zebrafish cultured cell lines in genetic toxicology is also on the rise [91,[97][98][99][100][101]. Up to now there have been more than 100 papers describing the zebrafish model both in vivo and in vitro using the comet assay for the assessment of different physical and/or chemical agents such as gamma rays [102,103], X-rays [104], pesticides [105], insecticides [106], fungicides [88,107], herbicides [108], mycotoxins [109], pharmaceuticals [98,99,[110][111][112], heavy metals A c c e p t e d M a n u s c r i p t 9 [108,113,114], PAHs [89], nanoparticles [115][116][117][118], flame retardants [119], sewage effluent [120], waste material [121] as well as model toxicants such as benzo(a)pyrene (B[a]P), methyl methanesulfonate (MMS) and ethyl methanesulfonate (EMS) [122,123].…”

Gamma radiation induces locus specific changes to histone modification enrichment in zebrafish and Atlantic salmon

“…Additionally, the histone PTM landscape has been described for this stage [29, 30]. We have recently described effects on the zebrafish embryo transcriptome after 3 h exposure to low dose rates (0.54, 5.4 and 10.9 mGy/h) of gamma radiation [5], as well as the short term and long term effects on the F1 embryo transcriptome after 27 days of parental exposures (8.7 and 53 mGy/h) [31, 32]. These studies also demonstrated adverse reproductive effects and genomic instability in F1 offspring [32].…”