Unfertilized frog eggs die by apoptosis following meiotic exit

Here, we report that the vast majority of naturally laid unfertilized eggs of the African clawed frog Xenopus laevis spontaneously exit metaphase arrest under various environmental conditions and degrade by a well-defined apoptotic process within 48 hours after ovulation. The main features of this process include cytochrome c release, caspase activation, ATP depletion, increase of ADP/ATP ratio, apoptotic nuclear morphology, progressive intracellular acidification, and egg swelling. Meiotic exit seems to be a prerequisite for execution of the apoptotic program, since (i) it precedes apoptosis, (ii) apoptotic events cannot be observed in the eggs maintaining high activity of MPF and CSF, and (iii) apoptosis in unfertilized frog eggs is accelerated upon early meiotic exit. The apoptotic features cannot be observed in the immature prophase-arrested oocytes, however, the maturation-inducing hormone progesterone renders oocytes susceptible to apoptosis.The study reveals that naturally laid intact frog eggs die by apoptosis if they are not fertilized. A maternal apoptotic program is evoked in frog oocytes upon maturation and executed after meiotic exit in unfertilized eggs. The meiotic exit is required for execution of the apoptotic program in eggs. The emerging anti-apoptotic role of meiotic metaphase arrest needs further investigation.The African clawed frog, Xenopus laevis, is an important model organism in developmental biology. Xenopus oocytes, eggs and early embryos have been widely used in cell cycle studies, which provided a basis for the current understanding of meiotic and mitotic transition. Most control mechanisms that operate in maturing oocytes, fertilized eggs, and early embryos have been first established in Xenopus laevis [reviewed in refs. [1,2]]. However, the fate of unfertilized eggs in this species has received little attention.Fully grown Xenopus oocytes of the stage VI are naturally arrested in the prophase of the first meiotic division with the int