Regulator of G-protein signaling 2 (RGS2) suppresses premature calcium release in mouse eggs

During oocyte maturation, capacity and sensitivity of Ca 2+ signaling machinery increases dramatically, preparing the metaphase II (MII)-arrested egg for fertilization. Upon sperm-egg fusion, Ca 2+ release from IP 3 -sensitive endoplasmic reticulum stores results in cytoplasmic Ca 2+ oscillations that drive egg activation and initiate early embryo development. Premature Ca 2+ release can cause parthenogenetic activation prior to fertilization; thus, preventing inappropriate Ca 2+ signaling is crucial for ensuring robust MII arrest. Here, we show that regulator of G-protein signaling 2 (RGS2) suppresses Ca 2+ release in MII eggs. Rgs2 mRNA was recruited for translation during oocyte maturation, resulting in ∼20-fold more RGS2 protein in MII eggs than in fully grown immature oocytes. Rgs2 -siRNA-injected oocytes matured to MII; however, they had increased sensitivity to low pH and acetylcholine (ACh), which caused inappropriate Ca 2+ release and premature egg activation. When matured in vitro , RGS2-depleted eggs underwent spontaneous Ca 2+ increases that were sufficient to cause premature zona pellucida conversion. Rgs2 −/− females had reduced litter sizes, and their eggs had increased sensitivity to low pH and ACh. Rgs2 −/− eggs also underwent premature zona pellucida conversion in vivo . These findings indicate that RGS2 functions as a brake to suppress premature Ca 2+ release in eggs that are poised on the brink of development.