Ovarian function in superoxide dismutase 1 and 2 knockout mice.
Copper/zinc superoxide dismutase (SOD1) and manganese superoxide dismutase (SOD2) are the two major intracellular enzymes which inactivate superoxide radicals. SOD1 is present in both cytoplasmic and nuclear compartments whereas SOD2 is localized to mitochondria. Both enzymes are expressed in multiple tissues as well as ovaries of several species including humans and rodents. Dominant mutations in SOD1 are associated with amyotrophic lateral sclerosis. We have previously demonstrated that SOD2-deficient mice die within three weeks of birth due to oxidative mitochondrial injury in central nervous system neurons and cardiac myocytes. In this report, we demonstrate that female homozygous mutant mice lacking SOD1 can survive to the adult stage but are subfertile. Whereas breeding of 5 SOD1 heterozygote females produced an average of 1.0 litter/month with 8.6 offspring/litter (n = 31 litters), only 11 of 16 SOD1 homozygote mice over a 2-6 month period became pregnant averaging 0.23 litters/month with an average litter size of 2.7 (n = 21 litters). Histological analysis of the ovaries from SOD1-deficient mice often reveals many primary and small antral follicles but few corpora lutea. In addition, ovaries from postnatal SOD2-deficient mice, transplanted to the bursa of wild-type hosts, show all stages of folliculogenesis including corpora lutea and can give rise to viable offspring. These studies support an important role of SOD1 in female reproductive function and suggest that SOD2 is not essential for ovarian function.
Department of Pathology, Baylor College of Medicine, Houston, TX 77030, USA. mmatzuk@bcm.tmc.edu
M M
MM
Matzuk
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Dionne
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Q
Guo
T R
TR
Kumar
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Lebovitz
D000818:Animals; D002460:Cell Line; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D007247:Infertility, Female / Q000235:genetics; D007527:Isoenzymes / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D010053:Ovary / Q000473:pathology / Q000502:physiology* / Q000637:transplantation; D011247:Pregnancy; D012098:Reproduction / Q000502:physiology; D013482:Superoxide Dismutase / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D007527:Isoenzymes; D013482:Superoxide Dismutase