Title: TRPM7 and CaV3.2 channels mediate Ca2+ influx required for egg activation at fertilization.
Authors: Bernhardt, Miranda L; Stein, Paula; Carvacho, Ingrid; Krapp, Christopher; Ardestani, Goli; Mehregan, Aujan; Umbach, David M; Bartolomei, Marisa S; Fissore, Rafael A; Williams, Carmen J
Published In Proc Natl Acad Sci U S A, (2018 10 30)
Abstract: The success of mammalian development following fertilization depends on a series of transient increases in egg cytoplasmic Ca2+, referred to as Ca2+ oscillations. Maintenance of these oscillations requires Ca2+ influx across the plasma membrane, which is mediated in part by T-type, CaV3.2 channels. Here we show using genetic mouse models that TRPM7 channels are required to support this Ca2+ influx. Eggs lacking both TRPM7 and CaV3.2 stop oscillating prematurely, indicating that together they are responsible for the majority of Ca2+ influx immediately following fertilization. Fertilized eggs lacking both channels also frequently display delayed resumption of Ca2+ oscillations, which appears to require sperm-egg fusion. TRPM7 and CaV3.2 channels almost completely account for Ca2+ influx observed following store depletion, a process previously attributed to canonical store-operated Ca2+ entry mediated by STIM/ORAI interactions. TRPM7 serves as a membrane sensor of extracellular Mg2+ and Ca2+ concentrations and mediates the effects of these ions on Ca2+ oscillation frequency. When bred to wild-type males, female mice carrying eggs lacking TRPM7 and CaV3.2 are subfertile, and their offspring have increased variance in postnatal weight. These in vivo findings confirm previous observations linking in vitro experimental alterations in Ca2+ oscillatory patterns with developmental potential and offspring growth. The identification of TRPM7 and CaV3.2 as key mediators of Ca2+ influx following fertilization provides a mechanistic basis for the rational design of culture media that optimize developmental potential in research animals, domestic animals, and humans.
PubMed ID: 30322909
MeSH Terms: Animals; Calcium Channels, T-Type/metabolism*; Calcium Signaling/physiology*; Calcium/metabolism*; Cell Membrane/metabolism; Cytoplasm/metabolism; Female; Fertilization/physiology*; Male; Mice; Mice, Inbred C57BL; Oocytes/metabolism; Spermatozoa/metabolism; Stromal Interaction Molecule 1/metabolism; TRPM Cation Channels/metabolism*; Zygote/metabolism*