title: Luteinizing hormone-dependent activation of the epidermal growth factor network is essential for ovulation.
abstract: In the preovulatory ovarian follicle, mammalian oocytes are maintained in prophase meiotic arrest until the luteinizing hormone (LH) surge induces reentry into the first meiotic division. Dramatic changes in the somatic cells surrounding the oocytes and in the follicular wall are also induced by LH and are necessary for ovulation. Here, we provide genetic evidence that LH-dependent transactivation of the epidermal growth factor receptor (EGFR) is indispensable for oocyte reentry into the meiotic cell cycle, for the synthesis of the extracellular matrix surrounding the oocyte that causes cumulus expansion, and for follicle rupture in vivo. Mice deficient in either amphiregulin or epiregulin, two EGFR ligands, display delayed or reduced oocyte maturation and cumulus expansion. In compound-mutant mice in which loss of one EGFR ligand is associated with decreased signaling from a hypomorphic allele of the EGFR, LH no longer signals oocyte meiotic resumption. Moreover, induction of genes involved in cumulus expansion and follicle rupture is compromised in these mice, resulting in impaired ovulation. Thus, these studies demonstrate that LH induction of epidermal growth factor-like growth factors and EGFR transactivation are essential for the regulation of a critical physiological process such as ovulation and provide new strategies for manipulation of fertility.
authors.affiliation: Division of Reproductive Biology, Department of Obstetrics and Gynecology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305-5317, USA.
authors.forename: Minnie
authors.initials: M
authors.lastname: Hsieh
authors.forename: Daekee
authors.initials: D
authors.lastname: Lee
authors.forename: Sara
authors.initials: S
authors.lastname: Panigone
authors.forename: Kathleen
authors.initials: K
authors.lastname: Horner
authors.forename: Ruby
authors.initials: R
authors.lastname: Chen
authors.forename: Alekos
authors.initials: A
authors.lastname: Theologis
authors.forename: David C
authors.initials: DC
authors.lastname: Lee
authors.forename: David W
authors.initials: DW
authors.lastname: Threadgill
authors.forename: Marco
authors.initials: M
authors.lastname: Conti
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000235:genetics / Q000502:physiology*; D005260:Female; D047468:Immunoprecipitation; D017403:In Situ Hybridization; D007986:Luteinizing Hormone / Q000378:metabolism / Q000494:pharmacology*; D008540:Meiosis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D009865:Oocytes / Q000166:cytology / Q000378:metabolism; D006080:Ovarian Follicle / Q000166:cytology; D010053:Ovary / Q000166:cytology; D010060:Ovulation / Q000502:physiology*; D015398:Signal Transduction; D013997:Time Factors
chemical_list: D006063:Chorionic Gonadotropin; D004815:Epidermal Growth Factor; D007986:Luteinizing Hormone