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BOR - Papers in Press, published online ahead of print April 20, 2005.
Biol Reprod 2005, 10.1095/biolreprod.105.040956
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BIOLOGY OF REPRODUCTION 73, 366–373 (2005)
DOI: 10.1095/biolreprod.105.040956
© 2005 by the Society for the Study of Reproduction, Inc.

Effect of Female Age on Mouse Oocyte Developmental Competence Following Mitochondrial Injury1

George A. Thouas 2 , Alan O. Trounson , and Gayle M. Jones 

Monash Immunology and Stem Cell Laboratories (MISCL), Monash University, Clayton, Victoria 3800, Australia

Oocytes from aging ovaries contain mitochondria with morphological and genetic flaws. How these flaws relate to phenotypes of oocyte developmental compromise associated with clinical infertility is not well understood. This study was conducted to investigate the role of mitochondria in the developmental compromises observed with female aging using a mouse model of mitochondrial dysfunction. Oocytes obtained from aging (30–40 wk) (C57BL/6J x CBACaH)F1 (B6CBAF1) hybrid female mice were photosensitized with mitochondrial fluorophore rhodamine-123 for variable durations and compared to similarly treated oocytes derived from pubertal mice (4–6 wk). Blastocyst development of normally fertilized oocytes from both age-groups correlated negatively in mathematically unique profiles with irradiation time, with a more sudden decline in development for oocytes from aging mice. Complete inhibition of blastocyst development occurred following a shorter duration of photosensitization for oocytes from aging compared to pubertal animals (60 vs. 90 sec). Prolonged photosensitization resulted in mitochondrial uncoupling and promoted localized generation of reactive oxygen species, mitochondrial permeabilization, and apoptotic phenotypes. Thus, aging oocytes are more developmentally sensitive to mitochondrial damage than pubertal oocytes but undergo similar metabolic and apoptotic responses. These and future findings may encourage further optimization of laboratory-based strategies to minimize mitochondrial injury to oocytes, particularly those from older women, and improve clinical outcomes for women with age-related etiologies of infertility.

aging, apoptosis, embryo, in vitro fertilization, oocyte development


1 Supported by departmental funding based on private donation, with scholarship support from the Helen Macpherson-Smith Trust.

2 Correspondence: George A. Thouas, Monash Immunology and Stem Cell Laboratories (MISCL), STRIP—Building 75, Monash University, Wellington Road, Clayton, VIC 3800, Australia. FAX: 61 3 9905 0680; george.thouas{at}med.monash.edu.au


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