Constitutive IPR1-mediated Ca release reduces Ca store content and stimulates mitochondrial metabolism in mouse GV oocytes.

In mammals, fertilization initiates Ca oscillations in metaphase II oocytes, which are required for the activation of embryo development. Germinal vesicle (GV) oocytes also display Ca oscillations, although these unfold spontaneously in the absence of any known agonist(s) and their function remains unclear. We found that the main intracellular store of Ca in GV oocytes, the endoplasmic reticulum ([Ca]), constitutively 'leaks' Ca through the type 1 inositol 1,4,5-trisphosphate receptor. The [Ca] leak ceases around the resumption of meiosis, the GV breakdown (GVBD) stage, which coincides with the first noticeable accumulation of Ca in the stores. It also concurs with downregulation of the Ca influx and termination of the oscillations, which seemed underpinned by the inactivation of the putative plasma membrane Ca channels. Lastly, we demonstrate that mitochondria take up Ca during the Ca oscillations, mounting their own oscillations that stimulate the mitochondrial redox state and increase the ATP levels of GV oocytes. These distinct features of Ca homeostasis in GV oocytes are likely to underpin the acquisition of both maturation and developmental competence, as well as fulfill stage-specific cellular functions during oocyte maturation.