Protective effect of Zymosan-A against radiation-induced premature ovarian insufficiency in a murine model.

Pelvic radiotherapy, a key treatment for pelvic malignancies, frequently causes iatrogenic premature ovarian insufficiency (POI) in young female patients, highlighting the urgent need for targeted, effective, and low-toxic radioprotectants. Zymosan-A, a TLR2/6 agonist, has potential radioprotective effects. We established a (60)Co γ-radiation-induced murine POI model and evaluated Zymosan-A's efficacy. Results showed Zymosan-A mitigated granulosa cell apoptosis, improved ovarian hormone levels and estrous cycle regularity, increased embryo number, and enhanced offspring weight. Its radioprotective effect against ovarian injury, mediated via the TLRs-NF-κB pathway, was abolished in TLR2-knockout mice. Thus, Zymosan-A effectively protects against radiotherapy-induced POI primarily through the TLR2-NF-κB pathway.