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BOR - Papers in Press, published online ahead of print July 21, 2004.
Biol Reprod 2004, 10.1095/biolreprod.104.028985
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Lin Liu
David L. Keefe
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Submitted February 25, 2004
Returned for revision March 17, 2004
Accepted July 1, 2004

Gamete Biology


Nuclear Origin of Aging-Associated Meiotic Defects in Senescence-Accelerated Mice

Lin Liu and David L. Keefe *

* To whom correspondence should be addressed. E-mail: dkeefe{at}wihri.org.

Abstract
Factors of both cytoplasmic and nuclear origin regulate metaphase chromosome alignment and spindle checkpoint during mitosis. Most aneuploidies associated with maternal aging are believed to derive from non-disjunction and meiotic errors, such as aberrations in spindle formation and chromosome alignment at meiosis I. Senescence-accelerated mice (SAM) exhibit aging-associated meiotic defects, specifically chromosome misalignment at meiosis I and II that resemble those found in human female aging. How maternal aging disrupts meiosis remains largely unexplained. Using germinal vesicle (GV) nuclear transfer, we found that aging-associated misalignment of metaphase chromosomes is predominately associated with the nuclear factors in the SAM model. Cytoplasm of young hybrid B6C3F1 mouse oocytes could partly rescue aging-associated meiotic chromosome misalignment, whereas cytoplasm of young SAM was ineffective in preventing the meiotic defects of old SAM oocytes, indicative of deficiency of SAM oocyte cytoplasm. Our results demonstrate that both nuclear and cytoplasmic factors contribute to the meiotic defects of the old SAM oocytes, and that the nuclear compartment plays the predominant role in the etiology of aging-related meiotic defects.

Key words: Gamete Biology • Aging • Developmental biology • Meiosis


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