Abstract
Kif4a, a member of the kinesin superfamily, has been reported to participate in a series of cellular processes such as chromosome condensation and cytokinesis during mitosis. However, the roles of KIF4a in meiosis are still unknown. In present study we found that the Kif4a protein expression decreased in maternal aged mouse oocytes. We then explored the roles of Kif4a in mouse oocyte meiosis by knockdown analysis. Kif4a was enriched at the spindle during mouse oocyte maturation. By specific knock down of the Kif4a using morpholino microinjection, we found that the disruption of Kif4a caused the failure of polar body extrusion. Further analysis indicated that Kif4a might affect the spindle morphology and chromosome alignment in the mouse oocytes, and this might be due to the regulation of tubulin acetylation. Moreover, our results showed that an increased proportion of aneuploidy in the Kif4a knock down oocytes, and this might be due to the loss of kinetochore-microtubule attachment. Taken together, these results suggested that Kif4a possibly regulated mouse oocyte meiosis through its effects on the spindle organization and accurate chromosome segregation, and the loss of Kif4a might be related with aneuploidy of aging oocytes.
Highlights
Kif4a, a member of the kinesin superfamily, has been reported to participate in a series of cellular processes such as chromosome condensation and cytokinesis during mitosis
We found that Kif4a expression was decreased in oocytes of aging mice
Our results provide evidence that Kif4a is important for aging-related aneuploidy in mouse oocytes
Summary
Kif4a, a member of the kinesin superfamily, has been reported to participate in a series of cellular processes such as chromosome condensation and cytokinesis during mitosis. Our results showed that an increased proportion of aneuploidy in the Kif4a knock down oocytes, and this might be due to the loss of kinetochore-microtubule attachment Taken together, these results suggested that Kif4a possibly regulated mouse oocyte meiosis through its effects on the spindle organization and accurate chromosome segregation, and the loss of Kif4a might be related with aneuploidy of aging oocytes. Fertilization of such aneuploid eggs may lead to embryonic aneuploidy, which is the main cause of miscarriage, implantation failure, and birth defects [6] Such spindle and chromosome defects become more prevalent as maternal age increases and are considered the major factors resulting in birth defects and an increased incidence of miscarriage [7, 8]. Functional analysis employing morpholino knockdown (KD) showed that Kif4a regulated spindle organization and chromosome alignment/segregation in mouse oocytes, indicating that loss of Kif4a is one reason for aneuploidy in aging oocytes. GV oocytes were cultured in M16 (Sigma) medium under mineral oil at 37°C in a 5% CO2 atmosphere
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