Constitutive IP3R1-mediated Ca2+ release reduces Ca2+ store content and stimulates mitochondrial metabolism in mouse GV oocytes

In mammals, fertilization initiates Ca2+ oscillations in metaphase II oocytes, which are required for the activation of embryo development. Germinal vesicle (GV) oocytes also display Ca2+ 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 Ca2+ in GV oocytes, the endoplasmic reticulum ([Ca2+]ER), constitutively ‘leaks’ Ca2+ through the type 1 inositol 1,4,5-trisphosphate receptor. The [Ca2+]ER leak ceases around the resumption of meiosis, the GV breakdown (GVBD) stage, which coincides with the first noticeable accumulation of Ca2+ in the stores. It also concurs with downregulation of the Ca2+ influx and termination of the oscillations, which seemed underpinned by the inactivation of the putative plasma membrane Ca2+ channels. Lastly, we demonstrate that mitochondria take up Ca2+ during the Ca2+ oscillations, mounting their own oscillations that stimulate the mitochondrial redox state and increase the ATP levels of GV oocytes. These distinct features of Ca2+ 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.