Regulation of Asymmetrical Cytokinesis by cAMP during Meiosis I in Mouse Oocytes

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.

Knockdown of PRKAR2B Results in the Failure of Oocyte Maturation

“…Thus, it can be inferred that PRKAR2B plays an important role in oocyte division. These results are consistent with previous reports that various factors, including PKA family proteins, play an important role in cell division of the oocyte meiosis stage [36, 37]. We also confirmed that PRKAR2B deficiency [38] results in division failure of the oocyte, as determined using time lapse video recording for 36 h (Fig.…”

Combined use of dbcAMP and IBMX minimizes the damage induced by a long‐term artificial meiotic arrest in mouse germinal vesicle oocytes

“…Oocytes treated with a single MAM reagent had larger PB1, this was consistent with previous results showing that the single use of dbcAMP, IBMX, or forskolin generated abnormal PB1 due to failed spindle migration (Chen et al, 2012). A high incidence of apoptosis is associated with a reduction in oocyte quality Wu et al, 2017).…”

“…Nevertheless, substantial evidence indicates that long‐term artificial MAM in oocytes by a single reagent induces unwanted adverse effects on the development potential of subsequent oocytes. For example, the artificial elevation of intracellular cAMP levels by dbcAMP or IBMX leads to a giant first polar body (PB1) in mice due to abnormal chromosome migration (Chen et al, 2012). Delayed oocyte maturation has been observed when forskolin or IBMX is used to maintain the GV stage in sheep (Buell, Chitwood, & Ross, 2015).…”

“…For example, the artificial elevation of intracellular cAMP levels by dbcAMP or IBMX leads to a giant first polar body (PB1) in mice due to abnormal chromosome migration (Chen et al, 2012). Delayed oocyte maturation has been observed when forskolin or IBMX is used to maintain the GV stage in sheep (Buell, Chitwood, & Ross, 2015).…”

Single cell transcriptome profiling revealed differences in gene expression during oocyte maturation in Haimen white goats

“…The stagnation of oocyte meiosis depends on high concentrations of second messenger cAMP (Chen et al, 2012) while the desired cAMP maintaining meiotic stagnant is produced by the oocyte itself (Liu et al, 2013). cAMP dependent protein kinase A inhibits maturation promoting factor (MPF) activity.…”