title: Expression of inositol 1,4,5-trisphosphate receptors in mouse oocytes and early embryos: the type I isoform is upregulated in oocytes and downregulated after fertilization.
abstract: A fertilization-induced increase in intracellular Ca2+ is responsible for initiating all of the events of egg activation. In mammals, the Ca2+ increase takes the form of a series of Ca2+ oscillations showing complex temporal and spatial properties. To understand the nature of these changes, we have investigated the expression patterns of the three isoforms of the inositol trisphosphate receptor (InsP3R) during oocyte maturation and preimplantation development. We find that mouse oocytes express mRNAs for all three InsP3R subtypes. Semiquantitative ratio reverse-transcriptase polymerase chain reaction shows that the type II isoform is the predominant message in mature oocytes, representing 67% of the InsP3R mRNA. In contrast, protein analysis reveals that the type I isoform accounts for all of the detectable InsP3R protein, despite representing only 20% of the InsP3R mRNA. The levels of InsP3R protein were examined to determine whether they correlated with the Ca2+ signaling events surrounding the fertilization process. Type I InsP3R protein increased during oocyte maturation and, in addition, within 8 h of fertilization underwent a dramatic decrease. During development to the blastocyst the level of type I InsP3R protein did not return to prefertilization levels and types II and III remained below our detection limit. The decrease in InsP3R protein after fertilization was found to correlate with a decrease in the sensitivity of InsP3-induced Ca2+ release. These studies show that the expression of InsP3R mRNA is developmentally regulated, that Ca2+ signaling at fertilization is mediated exclusively through the type I InsP3R, and that the InsP3R is downregulated after fertilization.
authors.affiliation: Department of Physiology, Department of Anatomy and Developmental Biology, University College London, Gower Street, London, WC1E 6BT, United Kingdom.
authors.forename: J
authors.initials: J
authors.lastname: Parrington
authors.forename: S
authors.initials: S
authors.lastname: Brind
authors.forename: H
authors.initials: H
authors.lastname: De Smedt
authors.forename: R
authors.initials: R
authors.lastname: Gangeswaran
authors.forename: F A
authors.initials: FA
authors.lastname: Lai
authors.forename: R
authors.initials: R
authors.lastname: Wojcikiewicz
authors.forename: J
authors.initials: J
authors.lastname: Carroll
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000235:genetics* / Q000502:physiology; D015536:Down-Regulation / Q000235:genetics*; D047108:Embryonic Development / Q000235:genetics; D005314:Embryonic and Fetal Development; D005260:Female; D005306:Fertilization / Q000502:physiology; D005455:Fluorescent Antibody Technique; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007527:Isoenzymes / Q000235:genetics*; D051379:Mice; D009865:Oocytes / Q000378:metabolism*; D011247:Pregnancy; D011506:Proteins / Q000032:analysis; D012333:RNA, Messenger / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics*
chemical_list: D015220:Calcium Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007527:Isoenzymes; D011506:Proteins; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium