TRPM7 and Ca3.2 channels mediate Ca influx required for egg activation at fertilization.

The success of mammalian development following fertilization depends on a series of transient increases in egg cytoplasmic Ca, referred to as Ca oscillations. Maintenance of these oscillations requires Ca influx across the plasma membrane, which is mediated in part by T-type, Ca3.2 channels. Here we show using genetic mouse models that TRPM7 channels are required to support this Ca influx. Eggs lacking both TRPM7 and Ca3.2 stop oscillating prematurely, indicating that together they are responsible for the majority of Ca influx immediately following fertilization. Fertilized eggs lacking both channels also frequently display delayed resumption of Ca oscillations, which appears to require sperm-egg fusion. TRPM7 and Ca3.2 channels almost completely account for Ca influx observed following store depletion, a process previously attributed to canonical store-operated Ca entry mediated by STIM/ORAI interactions. TRPM7 serves as a membrane sensor of extracellular Mg and Ca concentrations and mediates the effects of these ions on Ca oscillation frequency. When bred to wild-type males, female mice carrying eggs lacking TRPM7 and Ca3.2 are subfertile, and their offspring have increased variance in postnatal weight. These in vivo findings confirm previous observations linking in vitro experimental alterations in Ca oscillatory patterns with developmental potential and offspring growth. The identification of TRPM7 and Ca3.2 as key mediators of Ca 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.