Developmental effects of sublethal mitochondrial injury in mouse oocytes.
Mitochondrial dysfunction may be acquired or inherited by oocytes without detectable morphological abnormalities. This pathology may account for some examples of unexplained pregnancy loss in women following transfer of morphologically normal in vitro fertilization (IVF) embryos. The present study was intended to determine whether sublethal mitochondrial injury in mouse oocytes before IVF negatively affects pre- and postimplantation development, and to further define the latency of developmental compromise in relation to aberrant mitochondrial metabolism. Mature mouse oocytes were loaded with the mitochondrial fluorophore rhodamine-123 and photosensitized for 20 sec, a duration previously found to permit preimplantation embryo development to the blastocyst stage and so deemed "sublethal." This treatment resulted in some aberrations in cytoplasmic patterning of organelles, but did not inhibit zygote mitochondrial metabolism. Blastocyst development following IVF was not significantly inhibited following sublethal oocyte photosensitization; however, a decrease in trophectoderm cell numbers was observed relative to untreated controls. Following intrauterine transfer, blastocysts derived from sublethally photosensitized oocytes implanted but later aborted at a higher rate, formed fetuses with lower average weights, and, in rare cases, formed abnormal fetuses relative to controls. Photosensitization for more prolonged durations resulted in failed fertilization (2 min) and rapid oocyte degeneration (10 min). Therefore, photosensitization duration and the consequent degree of mitochondrial dysfunction are negatively related to the onset of developmental compromise. Acquired low-level mitochondrial injury is heritable by the resultant embryos and can cause postimplantation developmental compromise that may be relevant to some clinically observed outcomes following human assisted reproduction strategies, including reduced birth weights for gestational age. Future strategies for the detection and prevention of mitochondrial dysfunction may assist in improving outcomes for some clinically infertile women.
Thouas
George A
GA
Monash Immunology and Stem Cell Laboratories (MISCL), Monash University, Clayton, Victoria 3800, Australia. george.thouas@med.monash.edu.au
Trounson
Alan O
AO
Jones
Gayle M
GM
D000818:Animals; D001755:Blastocyst / Q000502:physiology; D047108:Embryonic Development / Q000528:radiation effects*; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D009865:Oocytes / Q000254:growth & development / Q000528:radiation effects*; D017319:Photosensitizing Agents; D015053:Zygote / Q000473:pathology
D017319:Photosensitizing Agents