Embryonic Poly(A)-Binding Protein (EPAB) Is Required for Granulosa Cell EGF Signaling and Cumulus Expansion in Female Mice.
Embryonic poly(A)-binding protein (EPAB) is the predominant poly(A)-binding protein in Xenopus, mouse, and human oocytes and early embryos before zygotic genome activation. EPAB is required for translational activation of maternally stored mRNAs in the oocyte and Epab(-/-) female mice are infertile due to impaired oocyte maturation, cumulus expansion, and ovulation. The aim of this study was to characterize the mechanism of follicular somatic cell dysfunction in Epab(-/-) mice. Using a coculture system of oocytectomized cumulus oophorus complexes (OOXs) with denuded oocytes, we found that when wild-type OOXs were cocultured with Epab(-/-) oocytes, or when Epab(-/-) OOXs were cocultured with WT oocytes, cumulus expansion failed to occur in response to epidermal growth factor (EGF). This finding suggests that oocytes and cumulus cells (CCs) from Epab(-/-) mice fail to send and receive the necessary signals required for cumulus expansion. The abnormalities in Epab(-/-) CCs are not due to lower expression of the oocyte-derived factors growth differentiation factor 9 or bone morphogenetic protein 15, because Epab(-/-) oocytes express these proteins at comparable levels with WT. Epab(-/-) granulosa cells (GCs) exhibit decreased levels of phosphorylated MEK1/2, ERK1/2, and p90 ribosomal S6 kinase in response to lutenizing hormone and EGF treatment, as well as decreased phosphorylation of the EGF receptor. In conclusion, EPAB, which is oocyte specific, is required for the ability of CCs and GCs to become responsive to LH and EGF signaling. These results emphasize the importance of oocyte-somatic communication for GC and CC function.
Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, New Haven, Connecticut 06510.
Cai-Rong
CR
Yang
Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, New Haven, Connecticut 06510.
Katie M
KM
Lowther
Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, New Haven, Connecticut 06510.
Maria D
MD
Lalioti
Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, New Haven, Connecticut 06510.
Emre
E
Seli
D000818:Animals; D055430:Bone Morphogenetic Protein 15 / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D054885:Cumulus Cells / Q000166:cytology / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000378:metabolism*; D066246:ErbB Receptors / Q000819:agonists* / Q000378:metabolism; D005260:Female; D006107:Granulosa Cells / Q000166:cytology / Q000378:metabolism*; D055429:Growth Differentiation Factor 9 / Q000378:metabolism; D007986:Luteinizing Hormone / Q000378:metabolism; D020935:MAP Kinase Signaling System; D018345:Mice, Knockout; D009865:Oocytes / Q000166:cytology / Q000378:metabolism*; D010766:Phosphorylation; D039102:Poly(A)-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D011974:Receptors, LH / Q000819:agonists / Q000378:metabolism; D015398:Signal Transduction
C525902:Bmp15 protein, mouse; D055430:Bone Morphogenetic Protein 15; C575837:EPAB protein, mouse; C525898:Gdf9 protein, mouse; D055429:Growth Differentiation Factor 9; D039102:Poly(A)-Binding Proteins; D011974:Receptors, LH; D004815:Epidermal Growth Factor; D007986:Luteinizing Hormone; C541485:EGFR protein, mouse; D066246:ErbB Receptors