title: Embryonic poly(A)-binding protein (EPAB) is required for oocyte maturation and female fertility in mice.
abstract: Gene expression during oocyte maturation and early embryogenesis up to zygotic genome activation requires translational activation of maternally-derived mRNAs. EPAB [embryonic poly(A)-binding protein] is the predominant poly(A)-binding protein during this period in Xenopus, mouse and human. In Xenopus oocytes, ePAB stabilizes maternal mRNAs and promotes their translation. To assess the role of EPAB in mammalian reproduction, we generated Epab-knockout mice. Although Epab(-/-) males and Epab(+/-) of both sexes were fertile, Epab(-/-) female mice were infertile, and could not generate embryos or mature oocytes in vivo or in vitro. Epab(-/-) oocytes failed to achieve translational activation of maternally-stored mRNAs upon stimulation of oocyte maturation, including Ccnb1 (cyclin B1) and Dazl (deleted in azoospermia-like) mRNAs. Microinjection of Epab mRNA into Epab(-/-) germinal vesicle stage oocytes did not rescue maturation, suggesting that EPAB is also required for earlier stages of oogenesis. In addition, late antral follicles in the ovaries of Epab(-/-) mice exhibited impaired cumulus expansion, and a 8-fold decrease in ovulation, associated with a significant down-regulation of mRNAs encoding the EGF (epidermal growth factor)-like growth factors Areg (amphiregulin), Ereg (epiregulin) and Btc (betacellulin), and their downstream regulators, Ptgs2 (prostaglandin synthase 2), Has2 (hyaluronan synthase 2) and Tnfaip6 (tumour necrosis factor α-induced protein 6). The findings from the present study indicate that EPAB is necessary for oogenesis, folliculogenesis and female fertility in mice.
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, 310 Cedar Street, LSOG 304D, New Haven, CT 06520, USA.
authors.forename: Ozlem
authors.initials: O
authors.lastname: Guzeloglu-Kayisli
authors.forename: Maria D
authors.initials: MD
authors.lastname: Lalioti
authors.forename: Fulya
authors.initials: F
authors.lastname: Aydiner
authors.forename: Isaac
authors.initials: I
authors.lastname: Sasson
authors.forename: Orkan
authors.initials: O
authors.lastname: Ilbay
authors.forename: Denny
authors.initials: D
authors.lastname: Sakkas
authors.forename: Katie M
authors.initials: KM
authors.lastname: Lowther
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Mehlmann
authors.forename: Emre
authors.initials: E
authors.lastname: Seli
mesh_terms: D000818:Animals; D001483:Base Sequence; D056744:Cyclin B1; D005260:Female; D005298:Fertility / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation; D007247:Infertility, Female / Q000235:genetics; D008297:Male; D008677:Metaphase / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009865:Oocytes / Q000502:physiology*; D009866:Oogenesis / Q000502:physiology; D006080:Ovarian Follicle / Q000502:physiology; D010060:Ovulation / Q000235:genetics; D039122:Poly(A)-Binding Protein I / Q000235:genetics; D039102:Poly(A)-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D026723:Polyadenylation; D008941:Spindle Apparatus / Q000235:genetics
chemical_list: C534700:Ccnb1 protein, mouse; D056744:Cyclin B1; C575837:EPAB protein, mouse; D039122:Poly(A)-Binding Protein I; D039102:Poly(A)-Binding Proteins