Oxidative stress dynamics during the estrous cycle: histological and biochemical findings in a rat model

Oxidative stress plays a crucial role in ovarian physiology and pathology, yet its dynamic changes across the estrous cycle remain unclear. This study aimed to investigate oxidative stress in rat ovarian tissue during the stages of the estrous cycle through histological and biochemical analyses. Vaginal smears identified estrous cycle stages, and ovarian tissues were examined histologically under a light microscope. Follicle counts, corpus luteum (CL) classification, oxidative stress marker (8-hydroxy-2'-deoxyguanosine/8-OHdG) staining, and apoptotic activity (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-nick end labeling/TUNEL) staining were analyzed. Serum malondialdehyde (MDA) and superoxide dismutase (SOD) activity was measured. Results showed strong 8-OHdG positivity in follicular epithelial cells surrounding the oocyte, granulosa cells of antral follicles, and CL cells. The detection of 8-OHdG positivity in CL cells, in both the nuclei and cytoplasm, suggests that oxidative stress affects both nuclear and mitochondrial DNA. Serum MDA levels were highest during estrus, while SOD activity was highest during metestrus. The increase in oxidative stress was associated with ovulation during estrus, while variations in SOD activity reflected changing defense mechanisms throughout the cycle. 8-OHdG positivity was high in follicular and luteal cells during CL regression, indicating ROS impact on follicular development and luteal function. Apoptotic cells were present mainly in antral follicles and luteal cells. These findings highlight the critical role of oxidative stress in ovarian function, with potential implications for fertility regulation and reproductive medicine. With rising oxidative stress levels, alternative cell death mechanisms likely contribute alongside apoptosis during CL regression.