The production of a mature vertebrate egg is a lengthy process in which the developing oocyte undergoes meiotic arrest followed by a long incubation period, before finally resuming meiosis in preparation for ovulation. The prevailing dogma in the field has been that, in Xenopus, meiotic arrest is released through a drop in cyclic adenosine monophosphate (cAMP) levels and protein kinase A (PKA) activity, which occurs following exposure to progesterone. In this issue (p. ), Khaled Machaca and colleagues provide evidence that challenges this dogma, as they demonstrate that no change is detectable in cAMP levels and PKA activity as meiotic arrest is released in the Xenopus oocyte. The authors use in vivo reporters to detect cAMP and PKA levels in real time in single cells, and show that there is no correlation between the rate of meiotic resumption and levels of cAMP or PKA inhibition. Furthermore, the authors develop conditions in which meiotic release is indeed possible in the presence of high levels of cAMP. These surprising results provide a new model for the release of meiotic arrest in the Xenopus oocyte and suggest that this phenomenon occurs through a positive signal downstream of the progesterone receptor that overcomes cAMP/PKA inhibition of meiosis resumption.
