CPEB controls oocyte growth and follicle development in the mouse.
CPEB is a sequence-specific RNA-binding protein that regulates polyadenylation-induced translation. In Cpeb knockout mice, meiotic progression is disrupted at pachytene due to inhibited translation of synaptonemal complex protein mRNAs. To assess the function of CPEB after pachytene, we used the zona pellucida 3 (Zp3) promoter to generate transgenic mice expressing siRNA that induce the destruction of Cpeb mRNA. Oocytes from these animals do not develop normally; they undergo parthenogenetic cell division in the ovary, exhibit abnormal polar bodies, are detached from the cumulus granulosa cell layer, and display spindle and nuclear anomalies. In addition, many follicles contain apoptotic granulosa cells. CPEB binds several oocyte mRNAs, including Smad1, Smad5, spindlin, Bub1b, Mos, H1foo, Obox1, Dnmt1o, TiParp, Trim61 and Gdf9, a well described oocyte-expressed growth factor that is necessary for follicle development. In Cpeb knockdown oocytes, Gdf9 RNA has a shortened poly(A) tail and reduced expression. These data indicate that CPEB controls the expression of Gdf9 mRNA, which in turn is necessary for oocyte-follicle development. Finally, several phenotypes, i.e. progressive oocyte loss and infertility, elicited by the knockdown of CPEB in oocytes resemble those of the human premature ovarian failure syndrome.
Racki
Waldemar J
WJ
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Richter
Joel D
JD
D000818:Animals; D015153:Blotting, Western; D055430:Bone Morphogenetic Protein 15; D017931:DNA Primers; D005260:Female; D055429:Growth Differentiation Factor 9; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D009865:Oocytes / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D006080:Ovarian Follicle / Q000254:growth & development*; D012333:RNA, Messenger / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors; D039221:mRNA Cleavage and Polyadenylation Factors
D055430:Bone Morphogenetic Protein 15; D017931:DNA Primers; D055429:Growth Differentiation Factor 9; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; C525901:BMP15 protein, human; C525902:Bmp15 protein, mouse; C525897:GDF9 protein, human; C525898:Gdf9 protein, mouse; C490387:Cpeb1 protein, mouse; D014157:Transcription Factors; D039221:mRNA Cleavage and Polyadenylation Factors