Abstract
Previous studies suggested a causal link between pre-natal exposure to ionizing radiation and birth defects such as microphthalmos and exencephaly. In mice, these defects arise primarily after high-dose X-irradiation during early neurulation. However, the impact of sublethal (low) X-ray doses during this early developmental time window on adult behavior and morphology of central nervous system structures is not known. In addition, the efficacy of folic acid (FA) in preventing radiation-induced birth defects and persistent radiation-induced anomalies has remained unexplored. To assess the efficacy of FA in preventing radiation-induced defects, pregnant C57BL6/J mice were X-irradiated at embryonic day (E)7.5 and were fed FA-fortified food. FA partially prevented radiation-induced (1.0 Gy) anophthalmos, exencephaly and gastroschisis at E18, and reduced the number of pre-natal deaths, fetal weight loss and defects in the cervical vertebrae resulting from irradiation. Furthermore, FA food fortification counteracted radiation-induced impairments in vision and olfaction, which were evidenced after exposure to doses ≥0.1 Gy. These findings coincided with the observation of a reduction in thickness of the retinal ganglion cell and nerve fiber layer, and a decreased axial length of the eye following exposure to 0.5 Gy. Finally, MRI studies revealed a volumetric decrease of the hippocampus, striatum, thalamus, midbrain and pons following 0.5 Gy irradiation, which could be partially ameliorated after FA food fortification. Altogether, our study is the first to offer detailed insights into the long-term consequences of X-ray exposure during neurulation, and supports the use of FA as a radioprotectant and antiteratogen to counter the detrimental effects of X-ray exposure during this crucial period of gestation.
Highlights
Exposure to ionizing radiation during embryonic development has been linked to an increased risk of birth defects
We revealed a partial prevention of radiation-induced left-eye anophthalmos with both the 8 mg/kg folic acid (FA) (9.02 ± 3.40%) and 12 mg/kg FA (10.62 ± 2.74%) diets (Figure 1A)
Late fetal deaths, the incidence of resorptions, fetal weight and skeletal defects within the cervical and thoracal vertebrae were all negatively affected by 1.0 Gy X-irradiation at E7.5, which was in turn partially countered by FA
Summary
Exposure to ionizing radiation during embryonic development has been linked to an increased risk of birth defects. It was observed that the more recent Fukushima Daiichi nuclear power plant accident elicited no increase in birth defects and pre-natal mortality due to environmental radioisotope contamination (Fujimori et al, 2014), but subsequent papers debated this conclusion (Mangano and Sherman, 2015; Scherb et al, 2016). In contrast to these more recent observations, reports after the atomic bombings in Japan only mentioned an increased incidence of microcephaly and intellectual disability (Plummer, 1952; Neel and Schull, 1956). The above highlights the need to increase our knowledge about the effects of pre-natal irradiation on biological structures and functions
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have