Interfollicular communication among preovulatory follicles after luteinizing hormone signaling

Luteinizing hormone (LH) triggers the resumption of oocyte meiosis and ovulation in preovulatory ovarian follicles. These events have generally been viewed as autonomous responses occurring independently within each follicle. Here, however, we show that mouse preovulatory follicles can communicate with one another through an LH-induced paracrine signaling network. Isolated preovulatory follicles lacking LH receptors (Lhr-KO) resumed oocyte meiosis when co-cultured with LH-stimulated wildtype follicles, despite being unable to respond directly to LH. Oocytes within Lhr-KO follicles also resumed meiosis when exposed to conditioned medium from LH-treated wildtype follicles, demonstrating that diffusible factors mediate this interfollicular communication. Neutralizing antibodies against the epidermal growth factor receptor ligands epiregulin and amphiregulin inhibited the LH-induced interfollicular communication, identifying these LH-induced factors as key signaling molecules. Although epiregulin and amphiregulin are known to transmit LH signals within individual follicles, our findings indicate that they can also coordinate responses among neighboring follicles. Together, these results demonstrate that LH regulates a communication network between preovulatory follicles rather than acting solely at the level of individual follicles.