Neutron Irradiation of Late Mouse Embryos (15-19 Days) in Utero

Abstract

Pregnant female C57B1/6 mice were irradiated with a single whole-body dose of 0.5 Gy neutrons. The F1 hybrid embryos were exposed to the neutrons in utero on Day 17 +/- 2 of gestation. 178/439 (40.6%) of the irradiated fetuses and 26/217 (12%) of the control mice died within 2 weeks after birth. In both irradiated and control mice, most deaths (95 and 77%, respectively) occurred within 3 days of birth: most animals in both groups died on Day 2. There was no significant difference in the number of living young born per litter (7.2) between the neutron-irradiated mothers and their unirradiated controls. The irradiated mice weighed significantly less than their controls. On the first day after birth, body weights of mice irradiated in utero averaged only 85% of control weights. Body weights did not reach control levels until 6 months after birth. Several organs were weighed at regular intervals in both irradiated and control mice. Spleens and thymus glands showed no significant differences between the two groups. The livers and kidneys of the irradiated mice weighed slightly less than their controls. The brain weight of 21-day-old neutron-irradiated mice was 30-35% less than control brains. The weight loss of the brain was not only a relative loss, but also an absolute one, based on brain weight/body weight ratios. Histological analysis of the central nervous system showed pycnotic nuclei, inhibition of mitosis in neuroblasts, and cell death in the irradiated brains. The weight reduction of the brain was not due to water loss. Our hypothesis is that the early mortality after birth is related to the killing of the radiation-sensitive neuroblasts. When newborn mice (1-7 days old) were irradiated in vivo with the same neutron dose of 0.5 Gy, neither the reduction in brain weight nor the early mortality was observed. The early deaths of the neutron-irradiated mouse embryos does not appear to be caused by either the hematological or the gastrointestinal radiation syndrome.

Postnatal Changes in Mice Exposed In Utero to Fast Neutrons

“…Other than the brain changes, while several organs and tissues weights were decreased, atrophic changes were only seen in the genital organs of the high dose groups of neutrons, and also of gamma-rays. A decrease of testis weight was also reported by Vogel et al 12 in BDF1 mice prenatally irradiated with neutrons. Though the mechanisms of testicular atrophy observed in this study was obscure at the present, examination on the early changes in the testis, such as cell death of spermatogonia, may provide us some information about its mechanism.…”

“…Neuro-hormonal regulation such as growth hormones, or cell proliferation regulation and/or apoptosis in those organs and tissues may be involved in their mechanisms. On the other hand, Vogel et al 12 reported that decreases of the body weight and the brain weight were much more significant in the mice irradiated at E17 than in the mice irradiated at E15, so that the pathological examination of early cell death and cell growth inhibition in the organs and tissues, in relation to the developmental phase, may provide us good information about the mechanisms and characteristics of the underdevelopment of mice prenatally exposed to neutrons.…”

“…Several studies have demonstrated that prenatal exposure to low-LET radiation induced abnormalities of the developing brain such as cerebral hypoplasia [5][6][7] and neuronal cell death 8,9 , and deceleration of neuronal migration 10,11 in rodents. As for neutrons, Vogel and his colleagues examined the changes of brain in mice prenatally exposed to 0.5 Gy of fission neutrons [12][13][14] , and showed that the body weight and the brain weight decreased induced in the irradiated mice 12,13 . Regarding the mechanism, they showed that the damage to the brain of the fetus after neutron irradiation was mainly due to killing and /or inhibition of the differentiation of neuroblasts 13 , and inhibition of protein synthesis was also observed in the irradiated brain 14 .…”

“…The histopathological differences from those reports may be related to the strain difference or type of radiation. Vogel et al 12 and Antal et al 13 examined the abnormalities of brain development in BDF1 mice i r r a d i a t e d w i t h 0 . 5 G y o f f i s s i o n n e u t r o n s w i t h contamination of 0.18 Gy of gamma-rays at E17, and showed remarkable decreases of the brain weight and the body weight in the irradiated mice, however the postnatal histopathological changes of the affected brains were not been determined.…”

Morphological changes in cultures of hippocampus following prenatal irradiation in the rat

“…The greatest sensitivity to radiation was found in early stages of prenatal development, mainly between weeks 8 and 15 of gestation (Dobbing and Sands, 1973;Antal et al, 1984;Vogel and Antal, 1984;Kameyama and Hoshino, 1Y86).…”