Investigating the Oocyte DNA Damage Response after Radiation Exposure

Michelle Seeler

Document Type

Article

Publication Date

Summer 2022

Keywords

JMG

JAX Location

In: Student Reports, Summer 2022, The Jackson Laboratory

Abstract

Primordial follicles (PFs), a population of follicles in the ovary which contain immature oocytes, are highly sensitive to DNA damage caused by cancer treatments. Ionizing radiation (IR) used as cancer treatment, induces DNA damage through double stranded breaks and reactive oxygen species resulting in extensive loss of PFs. The absence of these PFs can cause premature ovarian failure (POF) and infertility in cancer survivors. To prevent POF and infertility, new treatments need to be designed to preserve PFs long-term when the ovary is exposed to IR damage. Therefore, there is a need to understand how IR-induced damage leads to PF loss. The goal of this project is to investigate three potential signaling pathways and their role in PFs’ response to IR treatment. Preliminary data within the Bolcun-Filas lab indicate that the pathways of NF-kB signaling, FOXO3a signaling, and oxidative stress response may be involved in the PFs response to IR-induced damage. To test this hypothesis, protein localizations via immunofluorescence assays were used to detect pathway activation within irradiated and non-irradiated ovarian samples. Through these assays, we identified a dose-dependent response to IR-induced damage for FOXO3a. Assays of NF-KB and oxidative stress were inconclusive and further assays are needed to understand their contributions to the PFs response to IR-induced DNA damage. Understanding if and how these pathways contribute to the IR-induced PF damage response may provide targets for pharmacological intervention to preserve PFs and prevent infertility as a result of IR treatment.

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