Dev121707 2633..2640

During oocyte maturation, capacity and sensitivity of Ca signaling machinery increases dramatically, preparing the metaphase II (MII)arrested egg for fertilization. Upon sperm-egg fusion, Ca release from IP3-sensitive endoplasmic reticulum stores results in cytoplasmic Ca oscillations that drive egg activation and initiate early embryo development. Premature Ca release can cause parthenogenetic activation prior to fertilization; thus, preventing inappropriate Ca signaling is crucial for ensuring robust MII arrest. Here, we show that regulator of G-protein signaling 2 (RGS2) suppresses Ca release in MII eggs. Rgs2 mRNA was recruited for translation during oocytematuration, resulting in∼20-foldmoreRGS2 protein in MII eggs than in fully grown immature oocytes. Rgs2siRNA-injected oocytes matured to MII; however, they had increased sensitivity to low pH and acetylcholine (ACh), which caused inappropriate Ca release and premature egg activation. When matured in vitro, RGS2-depleted eggs underwent spontaneous Ca 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 release in eggs that are poised on the brink of