The overall aim of this proposal is to better understand the regulation of gene expression during mammalian oocyte and early embryo development. Oocyte maturation is associated with suppression of transcription. Consequently, gene expression during oocyte maturation, fertilization, and early embryo development until zygotic genome activation (ZGA), is regulated by translational activation of maternally- stored mRNAs. Embryonic poly(A) binding protein (ePAB) is the predominant poly(A) binding protein during Xenopus, mouse and human oocyte and early embryo development until ZGA. In Xenopus, ePAB is required for both known pathways (cytoplasmic polyadenylation-dependent and independent) that mediate maternal mRNA translational activation upon oocyte maturation. In addition, our preliminary findings demonstrate that oocyte maturation is inhibited when ePAB activity is suppressed in Xenopus oocytes, and that ePAB-deficient female mice are infertile due to impaired oogenesis. We therefore hypothesize that ePAB plays a key role in the regulation of gene expression during a critical period of early development, when transcription is suppressed. Here, we propose to characterize the cellular and molecular aspects of infertility in ePAB-deficient mice and to determine regulation of ePAB's function by phosphorylation.
The specific aims of this proposal are to: 1. Determine ePAB-null phenotype using a knockout mouse model. 2. Determine the role of ePAB phosphorylation in the regulation of maternal mRNA translational activation and oocyte maturation. These proposed studies focus on early development, and consequently the results obtained will have ramifications for human development and fertility.
The overall aim of this proposal is to better understand the regulation of gene expression during mammalian egg and early embryo development. Our ultimate goal is to characterize the molecular mechanisms responsible for important reproductive problems such as oocyte aging, and embryo loss. As a result of this enhanced understanding, development of targeted therapeutic strategies can ensue.
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|Babayev, Elnur; Wang, Tianren; Szigeti-Buck, Klara et al. (2016) Reproductive aging is associated with changes in oocyte mitochondrial dynamics, function, and mtDNA quantity. Maturitas 93:121-130|
|Yang, Cai-Rong; Lowther, Katie M; Lalioti, Maria D et al. (2016) Embryonic Poly(A)-Binding Protein (EPAB) Is Required for Granulosa Cell EGF Signaling and Cumulus Expansion in Female Mice. Endocrinology 157:405-16|
|Lowther, Katie M; Mehlmann, Lisa M (2015) Embryonic Poly(A)-Binding Protein Is Required During Early Stages of Mouse Oocyte Development for Chromatin Organization, Transcriptional Silencing, and Meiotic Competence. Biol Reprod 93:43|
|Garcia Velasco, Juan Antonio; Seli, Emre (2015) IVF: a short but exciting story. Curr Opin Obstet Gynecol 27:165-6|
|Ata, Baris; Seli, Emre (2015) Strategies for Controlled Ovarian Stimulation in the Setting of Ovarian Aging. Semin Reprod Med 33:436-48|
|Babayev, Elnur; Seli, Emre (2015) Oocyte mitochondrial function and reproduction. Curr Opin Obstet Gynecol 27:175-81|
|Seli, Emre; Babayev, Elnur; Collins, Stephen C et al. (2014) Minireview: Metabolism of female reproduction: regulatory mechanisms and clinical implications. Mol Endocrinol 28:790-804|
|Ozturk, Saffet; Guzeloglu-Kayisli, Ozlem; Lowther, Katie M et al. (2014) Epab is dispensable for mouse spermatogenesis and male fertility. Mol Reprod Dev 81:390|
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