This Article Full Text Full Text (PDF) All Versions of this Article: 20/4/715    most recent Author Manuscript (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Conti, M. Articles by Su, Y.-Q. Search for Related Content PubMed PubMed Citation Articles by Conti, M. Articles by Su, Y.-Q.

Role of the Epidermal Growth Factor Network in Ovarian Follicles

Division of Reproductive Biology, Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, California 94305

Address all correspondence and requests for reprints to: Marco Conti, Division of Reproductive Biology, Department of Obstetrics and Gynecology, Stanford University School of Medicine, 300 Pasteur Drive, Room A344, Stanford, California 94305-5317. E-mail: marco.conti{at}stanford.edu.

The LH surge causes major remodeling of the ovarian follicle in preparation for the ovulatory process. These changes include reprogramming of granulosa cells to differentiate into luteal cells, changes in cumulus cell secretory properties, and oocyte maturation. This review summarizes published data in support of the concept that LH stimulation of ovarian follicles involves activation of a local epidermal growth factor (EGF) network. A model describing this property of LH signaling and its branching to other signaling modules is discussed. According to this model, LH activation of mural granulosa cells stimulates cAMP signaling, which, in turn, induces the expression of the EGF-like growth factors epiregulin, amphiregulin, and betacellulin. These growth factors function by activating EGF receptors in either an autocrine/juxtacrine fashion within the mural layer, or they diffuse to act on cumulus cells. Activation of EGF receptor signaling in cumulus cells, together with cAMP priming, triggers oocyte nuclear maturation and acquisition of developmental competence as well as cumulus expansion. This model has important implications for ovarian physiology and for the development of new strategies for the pharmacological control of ovulation and for gamete maturation in vitro.

This article has been cited by other articles:

				M. Assidi, I. Dufort, A. Ali, M. Hamel, O. Algriany, S. Dielemann, and M.-A. Sirard Identification of Potential Markers of Oocyte Competence Expressed in Bovine Cumulus Cells Matured with Follicle-Stimulating Hormone and/or Phorbol Myristate Acetate In Vitro Biol Reprod, August 1, 2008; 79(2): 209 - 222. [Abstract] [Full Text] [PDF]

				M. P. Flynn, E. T. Maizels, A. B. Karlsson, T. McAvoy, J.-H. Ahn, A. C. Nairn, and M. Hunzicker-Dunn Luteinizing Hormone Receptor Activation in Ovarian Granulosa Cells Promotes Protein Kinase A-Dependent Dephosphorylation of Microtubule-Associated Protein 2D Mol. Endocrinol., July 1, 2008; 22(7): 1695 - 1710. [Abstract] [Full Text] [PDF]

				G. Ning, H. Ouyang, S. Wang, X. Chen, B. Xu, J. Yang, H. Zhang, M. Zhang, and G. Xia 3',5'-Cyclic Adenosine Monophosphate Response Element Binding Protein Up-Regulated Cytochrome P450 Lanosterol 14{alpha}-Demethylase Expression Involved in Follicle-Stimulating Hormone-Induced Mouse Oocyte Maturation Mol. Endocrinol., July 1, 2008; 22(7): 1682 - 1694. [Abstract] [Full Text] [PDF]

				X. Chen, B. Zhou, J. Yan, B. Xu, P. Tai, J. Li, S. Peng, M. Zhang, and G. Xia Epidermal growth factor receptor activation by protein kinase C is necessary for FSH-induced meiotic resumption in porcine cumulus-oocyte complexes J. Endocrinol., May 1, 2008; 197(2): 409 - 419. [Abstract] [Full Text] [PDF]

				E. Nagyova, A. Camaioni, R. Prochazka, A. J. Day, and A. Salustri Synthesis of Tumor Necrosis Factor Alpha-Induced Protein 6 in Porcine Preovulatory Follicles: A Study with A38 Antibody Biol Reprod, May 1, 2008; 78(5): 903 - 909. [Abstract] [Full Text] [PDF]

				K. T. Jones Meiosis in oocytes: predisposition to aneuploidy and its increased incidence with age Hum. Reprod. Update, March 1, 2008; 14(2): 143 - 158. [Abstract] [Full Text] [PDF]

				A. P.A. van Montfoort, J. P.M. Geraedts, J. C.M. Dumoulin, A. P.M. Stassen, J. L.H. Evers, and T. A.Y. Ayoubi Differential gene expression in cumulus cells as a prognostic indicator of embryo viability: a microarray analysis Mol. Hum. Reprod., March 1, 2008; 14(3): 157 - 168. [Abstract] [Full Text] [PDF]

				S. Cecconi, A. Mauro, G. Capacchietti, P. Berardinelli, N. Bernabo, A. R. Di Vincenzo, M. Mattioli, and B. Barboni Meiotic Maturation of Incompetent Prepubertal Sheep Oocytes Is Induced by Paracrine Factor(s) Released by Gonadotropin-Stimulated Oocyte-Cumulus Cell Complexes and Involves Mitogen-Activated Protein Kinase Activation Endocrinology, January 1, 2008; 149(1): 100 - 107. [Abstract] [Full Text] [PDF]

				A. A Gratao, M. Dahlhoff, F. Sinowatz, E. Wolf, and M. R Schneider Betacellulin Overexpression in the Mouse Ovary Leads to MAPK3/MAPK1 Hyperactivation and Reduces Litter Size by Impairing Fertilization Biol Reprod, January 1, 2008; 78(1): 43 - 52. [Abstract] [Full Text] [PDF]

				E. J. Joslin, L. K. Opresko, A. Wells, H. S. Wiley, and D. A. Lauffenburger EGF-receptor-mediated mammary epithelial cell migration is driven by sustained ERK signaling from autocrine stimulation J. Cell Sci., October 15, 2007; 120(20): 3688 - 3699. [Abstract] [Full Text] [PDF]

				C.-G. Liang, Y.-Q. Su, H.-Y. Fan, H. Schatten, and Q.-Y. Sun Mechanisms Regulating Oocyte Meiotic Resumption: Roles of Mitogen-Activated Protein Kinase Mol. Endocrinol., September 1, 2007; 21(9): 2037 - 2055. [Abstract] [Full Text] [PDF]

				S. Khambata-Ford, C. R. Garrett, N. J. Meropol, M. Basik, C. T. Harbison, S. Wu, T. W. Wong, X. Huang, C. H. Takimoto, A. K. Godwin, et al. Expression of Epiregulin and Amphiregulin and K-ras Mutation Status Predict Disease Control in Metastatic Colorectal Cancer Patients Treated With Cetuximab J. Clin. Oncol., August 1, 2007; 25(22): 3230 - 3237. [Abstract] [Full Text] [PDF]

				C. M. Wayne, H.-Y. Fan, X. Cheng, and J. S. Richards Follicle-Stimulating Hormone Induces Multiple Signaling Cascades: Evidence that Activation of Rous Sarcoma Oncogene, RAS, and the Epidermal Growth Factor Receptor Are Critical for Granulosa Cell Differentiation Mol. Endocrinol., August 1, 2007; 21(8): 1940 - 1957. [Abstract] [Full Text] [PDF]

				Y. Wang, J. Li, C. Ying Wang, A. H. Yan Kwok, and F. C. Leung Epidermal Growth Factor (EGF) Receptor Ligands in the Chicken Ovary: I. Evidence for Heparin-Binding EGF-Like Growth Factor (HB-EGF) as a Potential Oocyte-Derived Signal to Control Granulosa Cell Proliferation and HB-EGF and Kit Ligand Expression Endocrinology, July 1, 2007; 148(7): 3426 - 3440. [Abstract] [Full Text] [PDF]

				K.N. Fru, M. Cherian-Shaw, M. Puttabyatappa, C.A. VandeVoort, and C.L. Chaffin Regulation of granulosa cell proliferation and EGF-like ligands during the periovulatory interval in monkeys Hum. Reprod., May 1, 2007; 22(5): 1247 - 1252. [Abstract] [Full Text] [PDF]

				D. C Woods and A L Johnson Protein kinase C activity mediates LH-induced ErbB/Erk signaling in differentiated hen granulosa cells Reproduction, April 1, 2007; 133(4): 733 - 741. [Abstract] [Full Text] [PDF]

				T. Takahashi, J. D. Morrow, H. Wang, and S. K. Dey Cyclooxygenase-2-derived Prostaglandin E2 Directs Oocyte Maturation by Differentially Influencing Multiple Signaling Pathways J. Biol. Chem., December 1, 2006; 281(48): 37117 - 37129. [Abstract] [Full Text] [PDF]

				K. F. Rodriguez, L. A. Blomberg, K. A. Zuelke, J. R. Miles, J. E. Alexander, and C. E. Farin Identification of candidate mRNAs associated with gonadotropin-induced maturation of murine cumulus oocyte complexes using serial analysis of gene expression Physiol Genomics, November 21, 2006; 27(3): 318 - 327. [Abstract] [Full Text] [PDF]

				I. Ben-Ami, S. Freimann, L. Armon, A. Dantes, D. Strassburger, S. Friedler, A. Raziel, R. Seger, R. Ron-El, and A. Amsterdam PGE2 up-regulates EGF-like growth factor biosynthesis in human granulosa cells: new insights into the coordination between PGE2 and LH in ovulation Mol. Hum. Reprod., October 1, 2006; 12(10): 593 - 599. [Abstract] [Full Text] [PDF]

				I. Hernandez-Gonzalez, I. Gonzalez-Robayna, M. Shimada, C. M. Wayne, S. A. Ochsner, L. White, and J. S. Richards Gene Expression Profiles of Cumulus Cell Oocyte Complexes during Ovulation Reveal Cumulus Cells Express Neuronal and Immune-Related Genes: Does this Expand Their Role in the Ovulation Process? Mol. Endocrinol., June 1, 2006; 20(6): 1300 - 1321. [Abstract] [Full Text] [PDF]

				M. Shimada, I. Hernandez-Gonzalez, I. Gonzalez-Robayna, and J. S. Richards Paracrine and Autocrine Regulation of Epidermal Growth Factor-Like Factors in Cumulus Oocyte Complexes and Granulosa Cells: Key Roles for Prostaglandin Synthase 2 and Progesterone Receptor Mol. Endocrinol., June 1, 2006; 20(6): 1352 - 1365. [Abstract] [Full Text] [PDF]