UC Irvine

The biological effects of ionizing radiation on female reproduction have relatively been understudied. Currently about 30 percent of astronauts are women, and 46% of the 2017 NASA astronaut class are women. Astronauts are exposed to galactic cosmic rays (GCR) during travel in deep space. Galactic cosmic radiation is the dominant source of radiation that originates outside the earth’s solar system. And must be dealt with aboard current spacecraft and future space missions within our solar system. It permeates interplanetary space and can pass practically unimpeded through a spacecraft or the skin of an astronaut. GCR consist of protons, alpha particles, high-energy and highly charged ions called HZE particles and electrons. When GCR interacts with the gases within interstellar space, gamma radiation is also emitted. In assessing the reproductive toxicity risks to female astronauts, the premise that HZE particles have greater relative biological effectiveness than gamma radiation for ovarian toxicity has not been directly tested. Recently published studies investigated the effects of high LET 56Fe and 16O particles in mice of the same strain and age (Mishra et al., 2016 and 2017). Both studies demonstrated profound sensitivity of the ovary to high-LET charged ion irradiation, with more than half of the irreplaceable ovarian follicle reserve destroyed 1week after low dose irradiation. Comparison of prior studies suggest that high LET radiation may be a more potent inducer of ovarian follicle depletion than photon radiation, but existing published data sets did not utilize low enough doses of photon radiation to model the dose-response for these endpoints. In the current study, we present a comparison study investigating gamma radiation-induced dose dependent follicular destruction and relative biological effectiveness using same mice strain and age. 3-month-old female C57BL/6J mice were gamma-irradiated (0, 5, 15, and 50 cGy) using a 137Cs source and euthanized 1week after irradiation. Ovaries were collected and fixed in Bouin’s fixative at necropsy and were embedded in paraffin. Ovaries were then serially and completely sectioned at 5 µm thickness. Sections were stained with hematoxylin and eosin. Ovarian follicles were counted using light microscopy, blinded to the treatment group. We hypothesized that 1) gamma radiation will cause dose dependent ovotoxicity and morphological reduction in ovarian size and 2) ovarian follicle destruction from gamma radiation will be less potent than high charged high LET particle radiation. Result: 137Cs gamma radiation induced statistically significant reduction in measured total body in irradiated mice. Preliminary histomorphometric counts of 15 out of 32 ovaries shows 50cGy resulted in a dramatic total destruction of primordial and primary ovarian follicles after 1 week of irradiation, while follicle counts after 5 and 15 cGy did not differ from unirradiated controls.