Comparing Ovarian Reserve Damage Response to Different Sources of Radiation Exposure

Primordial follicles (PFs), a finite population of ovarian follicles containing an immature oocyte, are highly susceptible to damage. During genotoxic cancer treatment, the non-replenishable population of PFs may be damaged and eliminated from the ovary causing premature ovarian failure. To develop new treatments to preserve ovarian function, we need to understand how different sources of radiation damage PFs. Therefore, the goal of my research is to understand how gamma and x-ray radiation damages PFs. Ionizing radiation (IR) is used to treat cancer and some non-malignant diseases by inducing DNA double-strand breaks (DSBs) and oxidative stress. In radiobiology, gamma and x-ray radiation are considered similar because they do not emit any particles in their wavelength, instead, they emit radiation from energy changes in various parts of the atom which causes DNA damage directly by base oxidation, or by causing indirect damage through reactive oxygen species (Puy et al., 2021). While gamma and x-ray radiation are similar in most aspects there are known differences in their penetration depth and energy, which could result in varying amounts of direct or indirect damage, depending on which treatment is used and at what dose. The Bolcun-Filas Lab utilizes IR as a tool to define how oocytes respond to DNA damage to understand how oocytes are depleted from the ovary to develop ovarian preservation strategies. The Lab will be switching from gamma to x-ray radiation to continue their studies. THerefore, it is important to test whether radiation from two different sources elicits the same biological effect in ovaries. It is unknown how PFs respond to different clinically relevant sources of IR. This experiment will determine whether equivalent doses of gamma and X-ray IRinduce the same type and amount of damage in PFs. To determine how PFs respond to both gamma and X-ray IR, genetically sensitive (C57BL6/J) and resistant (Cast) mice were exposed to control (0gy), low dose (0.5Gy), and high dose (3Gy) of gamma and equivalent X-ray IR. Ovarian sections were immunostained for DSBs (gH2AX), DSB repair (RAD51), and oxidative stress (8-OHdG). The signal of these markers was quantified in PFs to determine how much damage is induced by different sources and doses of IR. We will discuss the results from our comparative study of the type and amount of damage occurring after IR in the oocytes of genetically sensitive and resistant mouse strains. The results from this study will define if a similar amount of damage is induced by different sources of radiation. Follow-up studies in the lab will assess the impact of X-ray radiation on PF survival. These results will establish if X-ray can be used in the lab instead of gamma radiation to further investigate radiation response in the ovary