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The present work investigates the multigenerational effects of paternal pre-conceptional exposure to continuous low-dose-rate gamma rays in C56BL/6J mice. Male C57BL/6J (F0 sires) mice were exposed to low dose rates of 20, 1, and 0.05 mGy/day for 400 days, to total accumulated doses of 8,000, 400, and 20 mGy, respectively. Upon completion of the radiation exposure, the F0 male mice were immediately bred to non-irradiated 8-week-old C57BL/6J females (F0 dams) to produce the first-generation (F1) mice. Randomly selected F1 males and females were then bred to produce the second-generation (F2) mice. All the mice, except the F0 dams, were subjected to pathological examination upon natural death. Reproductive parameters, lifespan, causes of death, neoplasm incidences and non-neoplastic disease incidences were used as parameters to evaluate the biological effects of continuous pre-conceptional exposure of the sires (F0) to continuous low-dose-rate radiation. There were no significant differences in the pregnancy and weaning rates among the parent (F0) generation. Average litter size and average number of weaned pups (F1) from dams bred to males (F0) exposed to 20 mGy/day were significantly decreased compared to the non-irradiated controls. Significant lifespan shortening in the sires (F0) was observed only in the 20 mGy/day group due to early death from malignant lymphomas. Life shortening was also observed in the F1 progeny of sires (F0) exposed to 20 and 1 mGy/day, but could not be attributed to a specific cause. No significant differences in the causes of death were found between dose groups in any generation. The number of primary tumors per mouse was significantly increased only in the F0 males exposed to 20 mGy/day. Except for the increased incidence rate for Harderian gland neoplasms in sires (F0) exposed to 20 mGy/day, there was no significant difference in neoplasm incidences and tumor spectra in all 3 generations in each sex regardless of radiation exposure. No multi- or transgenerational effects in the parameters examined were observed in the F1 and F2 progeny of sires exposed to 0.05 mGy/day for 400 days., (© 2024 by Radiation Research Society. All rights of reproduction in any form reserved.)

Previously, we reported that while low-dose-rate (LDR) gamma-ray exposure to 20 mGy/day for the entire gestation period (gestation days 0-18) did not result in any significant effect in B6C3F1 pups up to 10 weeks of age when compared to the non-irradiated controls, exposure to medium-dose-rates (MDR, 200 and 400 mGy/day) resulted in growth retardation and gonadal hypoplasia, in addition to delayed ossification (only at 400 mGy/day). In the present work, we investigated the late effects of continuous in utero exposure to gamma rays at LDRs (0.05, 1.0 and 20 mGy/day) and at an MDR of 400 mGy/day, on life span, causes of death, neoplastic and non-neoplastic disease incidences in B6C3F1 mice. Reproductive parameters such as litter size and weaning rates was not significantly different among the LDR groups, but was significantly decreased in the MDR group, when compared to the non-irradiated controls. Mean life spans were not significantly different among the LDR exposed groups compared to the non-irradiated controls, whereas the life spans of those exposed to the MDR were significantly shorter than the non-irradiated controls. There was no significant difference in tumor spectra between the non-irradiated and LDR nor MDR irradiated groups. In mice exposed to MDR in utero, the over-all incidence rates shifted with increased incidences in the number of neoplasms of liver (both sexes) and endocrine (adrenals, pituitary and ovaries in females) origin with corresponding decreases in the incidence of malignant lymphomas (both sexes) and lung neoplasms (males). Multiple primary neoplasms were significantly increased only in females exposed to MDR. Results show that B6C3F1 mice exposed to gamma-rays in utero at LDRs of 0.05, 1 and 20 mGy/day for the entire gestation period (18 days) does not significantly alter lifespan, cause of death, neoplasm incidence rates and tumor spectra., (©2022 by Radiation Research Society. All rights of reproduction in any form reserved.)

The effects of radiation exposure on germ cells and the gonads have been well studied at acute high-dose exposures, but the effects of chronic low-dose-rate (LDR) irradiation, particularly relevant for radiation protection, on germ cells and the gonads are largely unknown. Our previous study revealed that chronic exposure of mice to medium-dose-rate (MDR, 200 or 400 mGy/day) gamma-rays in utero for the entire gestation period (18 days) induced only a mild degree of general growth retardation, but with very drastic effects on the gonads and germ cells. In the current study, we further investigated the histomorphological changes in the gonads and the number of germ cells from gestation day (GD) 18 fetuses irradiated with MDR throughout the entire gestation period. The germ cells in the testes and ovaries of the MDR-irradiated fetuses were almost obliterated. Gestation day 18 fetuses exposed to LDR (20 mGy/day) radiation for the entire gestation period showed decreases in the number of the germ cells, which were not statistically significant or only marginally significant at most. Further investigations on the effects of LDR irradiation in utero using more sensitive methods are necessary., (©2021 by Radiation Research Society. All rights of reproduction in any form reserved.)