title: FSH Regulates mRNA Translation in Mouse Oocytes and Promotes Developmental Competence.
abstract: A major challenge in assisted reproductive technology is to develop conditions for in vitro oocyte maturation yielding high-quality eggs. Efforts are underway to assess whether known hormonal and local factors play a role in oocyte developmental competence and to identify the molecular mechanism involved. Here we have tested the hypothesis that FSH improves oocyte developmental competence by regulating the translational program in the oocyte. Accumulation of oocyte proteins (targeting protein for the Xenopus kinesin xklp2 and IL-7) associated with improved oocyte quality is increased when cumulus-oocyte complexes are incubated with FSH. This increase is due to enhanced translation of the corresponding mRNAs, as indicated by microinjection of constructs in which the 3' untranslated region of the Tpx2 or Il7 transcripts is fused to the luciferase reporter. A transient activation of the phosphatidyl-inositol 3-phosphate/AKT cascade in the oocyte preceded the increase in translation. When the epidermal growth factor (EGF) receptor is down-regulated in follicular cells, the FSH-induced rate of maternal mRNA translation and AKT activation were lost, demonstrating that the effects of FSH are indirect and require EGF receptor signaling in the somatic compartment. Using Pten(fl/fl):Zp3cre oocytes in which the AKT is constitutively activated, translation of reporters was increased and was no longer sensitive to FSH stimulation. More importantly, the oocytes lacking the phosphate and tensin homolog gene showed increased developmental competence, even when cultured in the absence of FSH or growth factors. Thus, we demonstrate that FSH intersects with the follicular EGF network to activate the phosphatidyl-inositol 3-phosphate/AKT cascade in the oocyte to control translation and developmental competence. These findings provide a molecular rationale for the use of FSH to improve egg quality.
authors.affiliation: Center for Reproductive Sciences (F.F., S.M., M.C.), Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research (F.F., M.C.), and Department of Obstetrics and Gynecology and Reproductive Sciences (F.F., M.C.), University of California, San Francisco, San Francisco, California 94143.
authors.forename: Federica
authors.initials: F
authors.lastname: Franciosi
authors.affiliation: Center for Reproductive Sciences (F.F., S.M., M.C.), Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research (F.F., M.C.), and Department of Obstetrics and Gynecology and Reproductive Sciences (F.F., M.C.), University of California, San Francisco, San Francisco, California 94143.
authors.forename: Shila
authors.initials: S
authors.lastname: Manandhar
authors.affiliation: Center for Reproductive Sciences (F.F., S.M., M.C.), Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research (F.F., M.C.), and Department of Obstetrics and Gynecology and Reproductive Sciences (F.F., M.C.), University of California, San Francisco, San Francisco, California 94143.
authors.forename: Marco
authors.initials: M
authors.lastname: Conti
mesh_terms: D000818:Animals; D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000187:drug effects* / Q000378:metabolism; D046149:Embryo Culture Techniques; D004797:Enzyme-Linked Immunosorbent Assay; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D005307:Fertilization in Vitro; D005640:Follicle Stimulating Hormone / Q000494:pharmacology*; D017930:Genes, Reporter; D006728:Hormones / Q000494:pharmacology*; D059471:In Vitro Oocyte Maturation Techniques; D015851:Interleukin-7 / Q000378:metabolism*; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000187:drug effects* / Q000378:metabolism; D009687:Nuclear Proteins / Q000187:drug effects* / Q000378:metabolism; D009865:Oocytes / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D010062:Ovulation Induction; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D014176:Protein Biosynthesis / Q000187:drug effects*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012333:RNA, Messenger / Q000187:drug effects* / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D018797:Cell Cycle Proteins; D006728:Hormones; D015851:Interleukin-7; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; C572046:TPX2 protein, mouse; D004815:Epidermal Growth Factor; D005640:Follicle Stimulating Hormone; D019869:Phosphatidylinositol 3-Kinases; C541485:EGFR protein, mouse; D066246:ErbB Receptors; D051057:Proto-Oncogene Proteins c-akt