DNA damage response signaling in oocytes from an oncofertility perspective†

Area of Science:

• Reproductive Biology
• Oncology
• Genetics

Background:

• Cancer therapies improve survival but often cause infertility in female survivors by depleting ovarian reserve.
• Oocytes are susceptible to DNA damage due to prolonged meiotic arrest, increasing risks over time.
• DNA damage response (DDR) normally eliminates damaged oocytes, but chemotherapy-induced damage is a major concern.

Purpose of the Study:

• To analyze the molecular mechanisms of DNA damage response (DDR) induced by anti-cancer agents in oocytes.
• To discuss knowledge gaps and future research directions for preserving ovarian reserve and fertility in young female cancer patients.

Main Methods:

• Review of molecular mechanisms underlying anti-cancer agent-induced DNA damage response in oocytes.
• Analysis of existing literature on DDR pathways in oocytes compared to somatic and cancer cells.

Main Results:

• Chemotherapeutic agents (doxorubicin, cisplatin, cyclophosphamide) and irradiation induce DNA damage in oocytes through various mechanisms.
• Genotoxic insults activate DDR in oocytes, leading to DNA repair or apoptosis.
• Precise DDR mechanisms in oocytes and their differences from somatic/cancer cells are not fully understood.

Conclusions:

• Understanding oocyte DDR is crucial for developing strategies to preserve fertility in cancer survivors.
• Further research is needed to elucidate specific DDR pathways in oocytes and identify therapeutic targets.