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1 August 2005 Effect of Female Age on Mouse Oocyte Developmental Competence Following Mitochondrial Injury
George A. Thouas, Alan O. Trounson, Gayle M. Jones
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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 × 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.

George A. Thouas, Alan O. Trounson, and Gayle M. Jones "Effect of Female Age on Mouse Oocyte Developmental Competence Following Mitochondrial Injury," Biology of Reproduction 73(2), 366-373, (1 August 2005).
Received: 13 February 2005; Accepted: 1 April 2005; Published: 1 August 2005

in vitro fertilization
oocyte development
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