• Open Access

Deficiency of ovarian ornithine decarboxylase contributes to aging-related egg aneuploidy in mice

Authors

  • Yong Tao,

    1. Ottawa Hospital Research Institute, Ottawa Hospital-General Campus, Ottawa, ON, Canada
    2. Faculty of Graduate and Postdoctoral Studies, University of Ottawa, Ottawa, ON, Canada
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  • X. Johné Liu

    Corresponding author
    1. Faculty of Graduate and Postdoctoral Studies, University of Ottawa, Ottawa, ON, Canada
    2. Department of Obstetrics and Gynaecology, University of Ottawa, Ottawa, ON, Canada
    3. Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON, Canada
    • Ottawa Hospital Research Institute, Ottawa Hospital-General Campus, Ottawa, ON, Canada
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Correspondence

X. Johné Liu, Ottawa Hospital Research Institute, The Ottawa Hospital - General Campus, 501 Smythe Road, box 511, Ottawa, K1H 6X9, Ontario. Tel: 613 798-5555 extn. 72906; Fax: 613 739-6968; e-mail: jliu@ohri.ca

Summary

It has been known for more than four decades that during mammalian estrous cycles, luteinizing hormone stimulates a transitory rise in the ovaries of ornithine decarboxylase (ODC) activity and its enzymatic product putrescine, concurrent with oocyte maturation in vivo. Inhibition of this transitory ODC/putrescine rise, however, does not appear to affect oocyte maturation or ovulation. Using several mouse models and combining in vitro and in vivo approaches, we demonstrated that deficiency of ODC during oocyte maturation is correlated with increased levels of egg aneuploidies. These results suggest that the transitory ovarian ODC rise in late proestrus is important for ensuring proper chromosome segregation during oocyte maturation. Older mice (8 months of age) exhibited about 1/3 that of young mice in LH-stimulated ovarian ODC activity and a corresponding increase in egg aneuploidies. Moreover, a combination of putrescine supplementation in mouse drinking water leading up to oocyte retrieval and in oocyte maturation medium reduced egg aneuploidies of the older mice from 12.7% to 5.3%. Therefore, ovarian ODC deficiency might be an important etiology of maternal aging-related aneuploidies, and peri-ovulatory putrescine supplementation might reduce the risk of aneuploid conceptions in older women.

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