Vincristine-induced alterations in ovarian function and oocyte quality: Modulation by dichloroacetate

Area of Science:

• Reproductive Biology
• Toxicology
• Oncology

Background:

• Vincristine (VCR) is a chemotherapy drug with generally low gonadotoxicity.
• Its precise impact on ovarian function and oocyte quality requires further investigation.
• Dichloroacetate (DCA), a metabolic modulator, may influence ovarian response to chemotherapy.

Purpose of the Study:

• To investigate the short-term and long-term effects of Vincristine (VCR) on ovarian function and oocyte quality in a mouse model.
• To evaluate the potential modulatory role of Dichloroacetate (DCA) in VCR-induced ovarian toxicity.

Main Methods:

• Adult female C57BL/6 mice were treated with VCR and/or DCA.
• Ovarian histology, immunohistochemistry (FOXO3a, AMH, cleaved caspase-3, Ki-67, oxidative stress markers), and oocyte assessments (number, diameter, meiotic spindle) were performed.
• Short-term (3 weeks) and long-term (7 weeks) effects were analyzed.

Main Results:

• VCR disrupted estrous cyclicity, reduced growing follicles, increased follicular atresia, decreased AMH, and increased FOXO3a cytoplasmic localization and ovarian catalase.
• Long-term VCR effects included reduced ovulation rate and altered oocyte diameter and meiotic spindle length.
• Combined VCR+DCA treatment exacerbated follicular loss and reduced ovulation rate, but some oocyte parameters improved.

Conclusions:

• Vincristine (VCR) causes significant and potentially persistent alterations in ovarian function and oocyte quality.
• Dichloroacetate (DCA) shows a dual effect, worsening follicular depletion but potentially improving certain oocyte morphology aspects.