922: Effects of near-continuous low-dose neutron irradiation on pregnancy outcomes in mice

Abstract

Now that orbital spaceflight is a continuous reality, deep space exploration and extra-Earth colonization have become the aspirational activities of space agencies and private entities. Understanding the impact of the extraterrestrial environment on human reproduction is a vital precursor to extra-Earth colonization, however, the effects of microgravity and cosmic radiation on reproductive physiology remain largely unknown. Relevant forms of cosmic radiation include protons, heavy ions, and the secondary neutron irradiation that occurs as protons bombard spacecrafts, habitats, or the human body, and these forms of radiation are fundamentally different than gamma or x-irradiation. We hypothesize that exposure of pregnant mice throughout gestation to chronic low-dose neutron irradiation would result in increased miscarriage and restricted fetal growth. Following copulatory plug positivity, eighty 9-13-week old female C57BL/6 mice were randomized to near-continuous neutron irradiation (21 hours/day) using Califonium-252 at a dose rate of 1 mGy/day vs. control (background: 0.005 mGy/day) for the duration of pregnancy (E0.5-E18.5) at NASA’s Colorado State University Neutron Radiation Facility. The dams were then randomized to euthanasia at either E12.5 to determine the rate of early miscarriage, or E18.5 to assess the rate of late miscarriage, fetal anomalies, and growth restriction. Placentas were weighed and stored for future secondary analyses including placental immunohistochemistry, cell signaling and nutrient transport, and gene expression studies. Phenotypic characteristics are provided in Table 1. Chronic low-dose neutron irradiation caused increased early resorption rate and significantly decreased placental weight. In contrast, there were no differences in birth length, birth weight, or anomaly rate between groups. Although this data cannot be directly extrapolated to humans, for the first time, we show that near-continuous low-dose neutron irradiation pan-pregnancy at a space-relevant dose rate leads to increased risk of miscarriage in a mouse model.