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Oocyte differentiation is genetically dissociable from meiosis in mice

Abstract

Oogenesis is the process by which ovarian germ cells undertake meiosis and differentiate to become eggs. In mice, Stra8 is required for the chromosomal events of meiosis to occur, but its role in differentiation remains unknown. Here we report Stra8-deficient ovarian germ cells that grow and differentiate into oocyte-like cells that synthesize zonae pellucidae, organize surrounding somatic cells into follicles, are ovulated in response to hormonal stimulation, undergo asymmetric cell division to produce a polar body and cleave to form two-cell embryos upon fertilization. These events occur without premeiotic chromosomal replication, sister chromatid cohesion, synapsis or recombination. Thus, oocyte growth and differentiation are genetically dissociable from the chromosomal events of meiosis. These findings open to study the independent contributions of meiosis and oocyte differentiation to the making of a functional egg.

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Figure 1: Stra8-deficient ovarian germ cells differentiate into oocyte-like cells.
Figure 2: A Stra8-deficient oocyte-like cell displays the ultrastructural features of a wild-type oocyte.
Figure 3: Stra8-deficient oocyte-like cells grow and differentiate without meiotic prophase.
Figure 4: Stra8-deficient oocyte-like cells organize ovulation-competent follicles.
Figure 5: Stra8-deficient oocyte-like cells divide asymmetrically upon maturation.
Figure 6: Premeiotic chromosome replication is dispensable for oocyte differentiation.
Figure 7: Stra8-deficient oocyte-like cells cleave to yield two-cell embryos upon fertilization.
Figure 8: A proposed model for the initiation of both meiosis (top) and oocyte growth and differentiation (bottom) in the mouse ovary.

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Acknowledgements

We thank C. Heyting (Agricultural University, Wageningen) for antiserum to REC8, N. Watson and L. Bechtold for assistance with electron microscopy and A. Amon, D. Bellott, M. Carmell, I. Cheeseman, D. de Rooij, R. Desgraz, T. Endo, G. Fink, M.A. Handel, T. Hassold, S. Hawley, A. Hochwagen, Y. Hu, J. Hughes, B. Lesch, J. Mueller, L. Okumura, T. Orr-Weaver, S. Repping, K. Romer and S. Soh for advice and comments on the manuscript. This work was supported by the Howard Hughes Medical Institute and the US National Institutes of Health (HD23839).

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G.A.D., A.E.B., J.J.E. and D.C.P. designed the experiments. G.A.D. and J.J.E. performed the experiments. G.A.D. and D.C.P. wrote the manuscript.

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Correspondence to David C Page.

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Dokshin, G., Baltus, A., Eppig, J. et al. Oocyte differentiation is genetically dissociable from meiosis in mice. Nat Genet 45, 877–883 (2013). https://doi.org/10.1038/ng.2672

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