title: Downregulation of store-operated Ca2+ entry during mammalian meiosis is required for the egg-to-embryo transition.
abstract: A specialized Ca(2+) transient at fertilization represents the universal driver for the egg-to-embryo transition. Ca(2+) signaling remodels during oocyte maturation to endow the egg with the capacity to produce the specialized Ca(2+) transient at fertilization, which takes the form of a single (e.g. Xenopus) or multiple (e.g. mouse) Ca(2+) spikes depending on the species. Store-operated Ca(2+) entry (SOCE) is the predominant Ca(2+) influx pathway in vertebrate oocytes, and in Xenopus SOCE completely inactivates during meiosis. Here, we show that SOCE is downregulated during mouse meiosis, but remains active in mature metaphase II eggs. SOCE inhibition is due to a decreased ability of the Ca(2+) sensor STIM1 to translocate to the cortical endoplasmic reticulum domain and due to internalization of Orai1. Reversing SOCE downregulation by overexpression of STIM1 and Orai1 prolongs the Ca(2+) oscillations at egg activation and disrupts the egg-to-embryo transition. Thus, SOCE downregulation during mammalian oocyte maturation is a crucial determinant of the fertilization-specific Ca(2+) transient, egg activation and early embryonic development.
authors: Center for Reproductive Medicine and Infertility, Weill Cornell Medical College, New York, NY 10021, USA.
authors: Bora
authors: B
authors: Lee
authors: Gianpiero
authors: G
authors: Palermo
authors: Khaled
authors: K
authors: Machaca
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D005260:Female; D005455:Fluorescent Antibody Technique; D008540:Meiosis / Q000187:drug effects / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D018613:Microscopy, Confocal; D000071740:ORAI1 Protein; D009865:Oocytes / Q000166:cytology / Q000187:drug effects; D010063:Ovum / Q000166:cytology* / Q000187:drug effects; D000071737:Stromal Interaction Molecule 1; D013324:Strontium / Q000494:pharmacology
chemical_list: D015220:Calcium Channels; D008562:Membrane Glycoproteins; D000071740:ORAI1 Protein; C520430:Orai1 protein, mouse; C520432:Orai3 protein, mouse; C100757:Stim1 protein, mouse; D000071737:Stromal Interaction Molecule 1; C025700:strontium chloride; D002118:Calcium; D013324:Strontium
keywords: Calcium oscillations; Egg-to-embryo transition; Mouse; Oocyte maturation; Orai1; STIM1; Store-operated calcium entry