AI Article Synopsis
- Oocyte aneuploidy is primarily caused by chromosome nondisjunction and sister chromatid issues, with topoisomerase II (TOP2) playing a significant but under-explored role in meiosis.
- Inhibiting TOP2 with agents like ICRF-193 or VP-16 during meiosis I disrupts chromatin condensation and causes arrests at metaphase I (MI), affecting the proper separation of chromosomes.
- The study found that interference with the spindle assembly checkpoint, Aurora B, or maturation-promoting factor can mitigate the negative effects of TOP2 inhibitors on oocyte maturation, indicating complex interactions that lead to failures in polar body abscission.
Article Abstract
Oocyte aneuploidy is caused mainly by chromosome nondisjunction and/or unbalanced sister chromatid pre-division. Although studies in somatic cells have shown that topoisomerase II (TOP2) plays important roles in chromosome condensation and timely separation of centromeres, little is known about its role during oocyte meiosis. Furthermore, because VP-16, which is a TOP2 inhibitor and induces DNA double strand breaks, is often used for ovarian cancer chemotherapy, its effects on oocytes must be studied for ovarian cancer patients to recover ovarian function following chemotherapy. This study showed that inhibiting TOP2 with either ICRF-193 or VP-16 during meiosis I impaired chromatin condensation, chromosome alignment, TOP2α localization, and caused metaphase I (MI) arrest and first polar body (PB1) abscission failure. Inhibiting or neutralizing either spindle assembly checkpoint (SAC), Aurora B or maturation-promoting factor (MPF) significantly abolished the effect of ICRF-193 or VP-16 on MI arrest. Treatment with ICRF-193 or VP-16 significantly activated MPF and SAC but the effect disappeared when Aurora B was inhibited. Most of the oocytes matured in the presence of ICRF-193 or VP-16 were arrested at MI, and only 11-27% showed PB1 protrusion. Furthermore, most of the PB1 protrusions formed in the presence of ICRF-193 or VP-16 were retracted after further culture for 7 h. In conclusion, TOP2 dysfunction causes MI arrest by activating Aurora B, SAC, and MPF, and it prevents PB1 abscission by promoting chromatin bridges.
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Topoisomerase II dysfunction causes metaphase I arrest by activating Aurora B, SAC and MPF and prevents PB1 abscission in mouse oocytes†.
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Article Synopsis
- Oocyte aneuploidy is primarily caused by chromosome nondisjunction and sister chromatid issues, with topoisomerase II (TOP2) playing a significant but under-explored role in meiosis.
- Inhibiting TOP2 with agents like ICRF-193 or VP-16 during meiosis I disrupts chromatin condensation and causes arrests at metaphase I (MI), affecting the proper separation of chromosomes.
- The study found that interference with the spindle assembly checkpoint, Aurora B, or maturation-promoting factor can mitigate the negative effects of TOP2 inhibitors on oocyte maturation, indicating complex interactions that lead to failures in polar body abscission.
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