BRCA1 deficiency in oocytes compromises ovulation without exacerbating follicle loss after chemotherapy in mice

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Research Question Does oocyte-specific loss of breast cancer susceptibility gene 1 (BRCA1) increase vulnerability to chemotherapy-induced ovarian damage in mice? Design We examined the effects of chemotherapeutic agents including cyclophosphamide, doxorubicin, paclitaxel, and carboplatin, on ovarian function in mice with oocyte-specific Brca1 deletion (cKO: Brca1 fl/fl Gdf9 cre/+ ) and wild-type controls (WT: Brca1 fl/fl Gdf9 +/+ ). Young (postnatal day 40-80) and reproductively older (postnatal day 180-220) mice received a single dose of chemotherapy or saline, and ovarian reserve, serum AMH, and ovulated oocytes were assessed. Results In young WT mice, doxorubicin significantly depleted primordial follicles ( p = 0.0082), whereas cyclophosphamide, paclitaxel, and carboplatin at the chosen doses did not significantly reduce primordial follicle numbers. Importantly, primordial follicle loss was not exacerbated by any chemotherapy in cKO mice versus WT. Follicle atresia and granulosa cell apoptosis were unaffected by treatment or genotype. In older mice, paclitaxel and carboplatin impaired superovulation and reduced mature MII oocyte yield in cKO mice, while ovarian reserve, including primordial and primary follicles, remained largely preserved. Conclusions These results indicate that Brca1 deficiency in mice reduced ovulatory capacity after chemotherapy in aged females without substantially altering follicle numbers. Our findings underscore the need to consider BRCA1 status in fertility preservation counselling and interventions for women undergoing chemotherapy.