Objective To explore the effect and mechanism of PLCγ1 in mouse oocyte meiotic resumption and to provide a reference for its study and clinical application in humans. Methods Real-time PCR was used to detect the mRNA expression levels of PLC isoforms in granulosa cells and cumulus cells. Models of follicle culture and cumulus-oocyte complexes (COCs) culture in vitro were generated to study the effect of U73122 (PLCγ1 specific inhibitor) on LH- and EGF-induced oocyte meiotic resumption. Changes in intracellular calcium levels were monitored using Fluo 3-AM, and cGMP levels were measured by ELISA. The expressions of IP₃R isoforms (mRNA and protein levels) were detected by Real-time PCR, Western blot, and immunohistochemistry. Results The expression of Plcγ1 mRNA levels in granulosa cells and cumulus cells was significantly higher than that of other isoforms ( P <0. 05). Furthermore, U73122 inhibited LH/ EGF-induced oocyte meiotic resumption ( P <0. 05) and decreased EGF-induced calcium levels in cumulus cells ( P < 0. 05). In addition, U73122 significantly reversed the decline of cGMP levels mediated by EGF ( P <0. 05). The expression of Itpr1 mRNA levels was significantly higher than other isoforms in granulosa cells, cumulus cells, and oocytes ( P < 0. 05). Western blot and immunohistochemistry showed that IP₃R1 protein was expressed in all the three cell types. Conclusions LH-dependent EGF receptor signaling increases calcium levels in cumulus cells through PLCγ1-IP₃R1, which ultimately induces meiotic resumption.