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

ABSTRACT: 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.

SUBMITTER: Wakai T 

PROVIDER: S-EPMC6382016 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature