Mitochondrial regulation of [Ca 2+]i oscillations during cell cycle resumption of the second meiosis of oocyte

Cell Cycle. 2018;17(12):1471-1486. doi: 10.1080/15384101.2018.1489179. Epub 2018 Jul 23.

Abstract

Oocyte is arrested at metaphase of the second meiosis until fertilization switching on [Ca2+]i oscillations. Oocyte activation inefficiency is the most challenging problem for failed fertilization and embryonic development. Mitochondrial function and intracellular [Ca2+]i oscillations are two critical factors for the oocyte's developmental potential. We aimed to understand the possible correlation between mitochondrial function and [Ca2+]i oscillations in oocytes. To this end, mitochondrial uncoupler CCCP which damages mitochondrial function and two small molecule mitochondrial agonists, L-carnitine (LC) and BGP-15, were used to examine the regulation of [Ca2+]i by mitochondrial functions. With increasing CCCP concentrations, [Ca2+]i oscillations were gradually diminished and high concentrations of CCCP led to oocyte death. LC enhanced mitochondrial membrane potential and [Ca2+]i oscillations and even improved the damage induced by CCCP, however, BGP-15 had no beneficial effect on oocyte activation. We have found that mitochondrial function plays a vital role in the generation of [Ca2+]i oscillations in oocytes, and thus mitochondria may interact with the ER to generate [Ca2+]i oscillations during oocyte activation. Improvement of mitochondrial functions with small molecules can be expected to improve oocyte activation and embryonic development in infertile patients without invasive micromanipulation.

Keywords: Oocyte activation; [Ca2+]i oscillations; mitochondria; mitochondrial membrane potential.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Calcium Signaling / physiology*
  • Carbonyl Cyanide m-Chlorophenyl Hydrazone / metabolism
  • Carnitine / metabolism
  • Cell Cycle / physiology
  • Embryonic Development / physiology
  • Female
  • Meiosis / physiology*
  • Mice
  • Mice, Inbred ICR
  • Mitochondria / metabolism*
  • Oocytes / metabolism*
  • Oogenesis / physiology
  • Oximes / metabolism
  • Piperidines / metabolism
  • Pregnancy

Substances

  • Oximes
  • Piperidines
  • Carbonyl Cyanide m-Chlorophenyl Hydrazone
  • BGP 15
  • Carnitine
  • Calcium

Grant support

This work was sponsored by National Natural Science Foundation of China (No 81671425). All authors of this study have no competing or financial interests to declare.