Article | Published:

Somatic cells regulate maternal mRNA translation and developmental competence of mouse oocytes

Nature Cell Biology volume 15, pages 14151423 (2013) | Download Citation

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Abstract

Germ cells divide and differentiate in a unique local microenvironment under the control of somatic cells. Signals released in this niche instruct oocyte reentry into the meiotic cell cycle. Once initiated, the progression through meiosis and the associated programme of maternal messenger RNA translation are thought to be cell autonomous. Here we show that translation of a subset of maternal mRNAs critical for embryo development is under the control of somatic cell inputs. Translation of specific maternal transcripts increases in oocytes cultured in association with somatic cells and is sensitive to EGF-like growth factors that act only on the somatic compartment. In mice deficient in amphiregulin, decreased fecundity and oocyte developmental competence is associated with defective translation of a subset of maternal mRNAs. These somatic cell signals that affect translation require activation of the PI(3)K–AKT–mTOR pathway. Thus, mRNA translation depends on somatic cell cues that are essential to reprogramme the oocyte for embryo development.

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Acknowledgements

We thank D. Laird, D. Ruggero, T. Nystul and R. Belloch at UCSF for advice during the studies and for critical reading of the manuscript, and A. Susor for assisting with the oocyte confocal microscopy analysis. This work was supported by Eunice Kennedy Shriver National Institute of Child Health and Human Development/NIH cooperative agreement 1U54HD055764-06, as part of the Specialized Cooperative Centers Program in Reproduction and Infertility Research, and RO1-GM097165 to M.C.

Author information

Affiliations

  1. Center for Reproductive Sciences, University of California, San Francisco, California 94143, USA

    • Jing Chen
    • , Simona Torcia
    • , Fang Xie
    • , Chih-Jen Lin
    • , Hakan Cakmak
    • , Federica Franciosi
    • , Kathleen Horner
    • , Courtney Onodera
    • , Jun S. Song
    • , Marcelle I. Cedars
    • , Miguel Ramalho-Santos
    •  & Marco Conti
  2. Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, California 94143, USA

    • Jing Chen
    • , Simona Torcia
    • , Fang Xie
    • , Chih-Jen Lin
    • , Hakan Cakmak
    • , Federica Franciosi
    • , Kathleen Horner
    • , Courtney Onodera
    • , Jun S. Song
    • , Miguel Ramalho-Santos
    •  & Marco Conti
  3. Department of Obstetrics and Gynecology and Reproductive Sciences, University of California, San Francisco, California 94143, USA

    • Jing Chen
    • , Simona Torcia
    • , Fang Xie
    • , Chih-Jen Lin
    • , Hakan Cakmak
    • , Federica Franciosi
    • , Kathleen Horner
    • , Marcelle I. Cedars
    • , Miguel Ramalho-Santos
    •  & Marco Conti
  4. Institute of Human Genetics, University of California, San Francisco, California 94143, USA

    • Courtney Onodera
    •  & Jun S. Song

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Contributions

J.C. developed the CEO translation assay and carried out the microarray experiments and some of the AKT assays; S.T. carried out the characterization of the Areg null phenotype; F.X. contributed with western blot studies and oocyte isolation for microinjection; C-J.L. helped with immunostaining experiments and the microinjections in cumulus oocyte complexes; H.C. carried out the experiments on protein secretion and contributed to the writing of the manuscript. F.F. carried out microinjections in CEOs; K.H. contributed with the preparation of the translational luciferase reporters; C.O. and J.S.S. carried out the bioinformatic analysis of the microarray data. M.I.C. advised on data analysis and discussed results; M.R-S. provided reagents and constructs and advised in the interpretation of the data; M.C. conceived the project, designed the experiments, analysed the data and wrote the paper.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Marco Conti.

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DOI

https://doi.org/10.1038/ncb2873

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