The Role Of NGF And Its Receptor In Regulation Of Mouse Follicular Development

TrkA, the high-affinity receptor of nerve growth factor (NGF), one of NTs family, is known to play key roles in ovarian follicular development, such as on assembling primordial follicles, promoting the early stages of follicular development, inducing the initial biochemical differentiation of secondary follicles into gonadotropin-responsive structures and facilitating ovulation. However, little is known about the roles of TrkA in cumulus oocyte complex (COCs) expansion.In this study, we found that TrkA was abundant in large antral follicles, so TrkA may play a role in the late stage of follicular development, such as cumulus expansion. Knockdown of TrkA in cumulus cells attenuated epidermal growth factor (EGF)-induced COCs expansion and further decreased the ovulation rate. So it is clear that TrkA participate in EGF-induced cumulus expansion. The effect of TrkA on COCs expansion was not mediated through downstream EGF effectors, phosphorylation of ERK1/2or SMAD, or through up-regulation of COCs expansion-related transcripts such as prostaglandin-endoperoxide synthase2(Ptgs2), hyaluronan synthase2(Has2), TNF-induced protein6(Tnfaip6) or pentraxin3(Ptx3). So there may be a new COCs expansion-related transcripts during this process. However, pharmacological blockade of TrkA transducing activity (K252a) in COCs decreased them RNA expression and protein secretion of interleukin-6(IL-6) in cumulus, identified from mRNA microarray of K252a-treated COCs. In addition, IL-6rescued the inhibitory effect of K252a on EGF-induced cumulus expansion, and on ovlation ratio. Furthermore, COCs expansion-related transcripts, as well as IL-6, also serve as inflammation-related genes in cumulus cells. Therefore, IL-6may act as a new potential cumulus expansion-related transcript, which may be involved in the integration of TrkA and EGF signaling in affecting COCs expansion. Here, we provide mechanistic insights into the roles of TrkA in EGF-induced cumulus expansion. Understanding potential cross-points between TrkA and EGF affecting cumulus expansion will help in the discovery of new therapeutic targets in ovulation-related diseases.