Teratology Society 57th Annual meeting_World Spotlight: Elevating Birth Defects Research

Ionizing radiation has become an intrinsic part of modern society. However, the aftermath of nuclear disasters and the atomic bombings have illustrated the deleterious effects on health as well. For example, congenital anomalies are shown to be induced after prenatal exposure to ionizing radiation. These defects are attributed to the high radiosensitivity of the unborn child, with defects being dependent on the dose and on the time of radiation exposure. In a previous study we identified embryonic day (E) 7.5, being the earliest stage of neural tube closure and eye development, as the most radiosensitive stage for inducing exencephaly and microphthalmos. Prenatal fortification with folic acid (FA) has previously been identified as an antiteratogen with the capacity to prevent malformations such as neural tube defects and heart defects. Considering the role of FA in DNA repair and its antioxidant capacity (both crucial in the biological response to radiation damage), we hypothesized that X-ray-induced defects might be classified as folate-responsive and that FA fortification could thus successfully prevent X-ray-induced malformations. To test this, C57/Bl6J mice were put on three different FA diets: 3.5 mg/kg (control), 10 mg/kg and 20 mg/kg FA, starting one week before coupling. Of note, we observed no apparent toxic effects of FA supplementation. Interestingly, FA fortification resulted in a significant decrease of radiation-induced microphthalmos, exencephaly, agnathia and open-eye in E18 fetuses irradiated with 1.0 Gy at E7.5. However, no dose response could be observed with the double fortification, suggesting that elevating the FA dose beyond the suggested dose in mice (10 mg/kg) holds no added value. Further molecular work to assess the mechanisms underlying this FA-induced radioprotection after irradiation at E7.5 is currently ongoing. In all, our group is the first to demonstrate the radioprotective role of FA in preventing various radiation-induced congenital defects, including microphthalmos. From a radiation protection viewpoint, our study thus supports food fortification with FA to prevent high-dose induced congenital defects. Moreover, we concur with literature to limit the fortification to the currently accepted optimal FA dose (10 mg/kg).