Abstract
Mammalian oocytes undergo an asymmetrical first meiotic division, extruding half of their chromosomes in a small polar body to preserve maternal resources for embryonic development. To divide asymmetrically, mammalian oocytes relocate chromosomes from the center of the cell to the cortex, but little is known about the underlying mechanisms. Here, we show that upon the elevation of intracellular cAMP level, mouse oocytes produced two daughter cells with similar sizes. This symmetrical cell division could be rescued by the inhibition of PKA, a cAMP-dependent protein kinase. Live cell imaging revealed that a symmetrically localized cleavage furrow resulted in symmetrical cell division. Detailed analyses demonstrated that symmetrically localized cleavage furrows were caused by the inappropriate central positioning of chromosome clusters at anaphase onset, indicating that chromosome cluster migration was impaired. Notably, high intracellular cAMP reduced myosin II activity, and the microinjection of phospho-myosin II antibody into the oocytes impeded chromosome migration and promoted symmetrical cell division. Our results support the hypothesis that cAMP plays a role in regulating asymmetrical cell division by modulating myosin II activity during mouse oocyte meiosis I, providing a novel insight into the regulation of female gamete formation in mammals.
Highlights
Asymmetrical cell division generates unequally sized daughter cells that are destined to acquire different fates
This study showed that the administration of chemicals that elevate intracellular cAMP caused some oocytes to undergo symmetrical cell division during meiosis I, producing two daughter cells with similar sizes
The activity of myosin II, downstream of the cAMP-PKA pathway, was decreased when intracellular cAMP was elevated and microinjection of oocytes with antibodies against activated myosin II severely impeded chromosome migration toward the cortex during meiosis I and resulted in symmetrical divisions. These results provide evidence that cAMP plays a role in modulating chromosome migration by regulating myosin II activity, subsequently affecting cleavage furrow localization and the asymmetrical division of meiosis I in oocytes
Summary
Asymmetrical cell division generates unequally sized daughter cells that are destined to acquire different fates. As the oocyte resumes meiosis in response to hormonal stimulation, it undergoes a process of meiotic maturation to complete meiosis I with an extreme form of asymmetrical cell division This produces the secondary oocyte and the much smaller first polar body [7,8,9,10]. The secondary oocyte is arrested at metaphase II until fertilization or parthenogenetic activation drives meiotic spindle II to rotate 90 degrees to facilitate the extrusion of the second polar body [11] During both meiosis I and II, cortical migration and asymmetrical positioning of the meiotic spindle is crucial for the asymmetry of the division [10,12]
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