Journal of Fertilization: In Vitro - IVF-Worldwide, Reproductive Medicine, Genetics & Stem Cell Biol
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Accumulation of Microsatellite Instability in Superoxide Dismutase-1 Knockout Mice: A Possible Predictor of Germ Cell Development or Tumorigenesis

Harold Moreno-Ortiz, Clara Esteban-Pérez, Elkin Lucena, Nancy A Reichert and Dwayne A Wise

The superoxide dismutase 1 gene (Sod1) is one of the cell protective mechanisms to eliminate reactive oxygen species damage in order to protect cell components and avoid germinal failure or tumorigenesis. Mouse primordial germinal cells are a population of cells originating from the proximal margin of the epiblast in close proximity to the extra embryonic ectoderm, and from which some cells differentiate into male or female germinal cells. During cell migration across the genital ridge, primordial germinal cells display an extensive proliferation rate and they are exposed to ROS damage. In absence of cell antioxidant mechanisms, primordial germinal cells have increased risk to accumulate specific mutations by free radical damage. We hypothesize that during cell migration, Sod1 knockout primordial germinal cells accumulate microsatellite instability and this could be a signal for primordial germinal cells pool selection, premature ovarian failure or tumor transformation. We dissected and isolated primordial germinal cellsfrom Sod1+/+ (wild type), Sod1+/- (heterozygous), and Sod1-/- (homozygous) mouse strain (B6; 129S7-Sod1tm1Leb/J), from the genital ridge at 10. 5 and 18 days post coitum to determine and quantify microsatellite instability in 10 single tandem repeat markers by single cell PCR methods. Our results demonstrate that primordial germinal cells from Sod1knockout mice accumulated microsatellite instability in five markers (4-4-19844, D13mit16, D13mit78, D19mit68, and DXmit249) located near important genes involved in cell proliferation and differentiation. Taken together, this study shows that microsatellite instability is directly related to Sod1 gene disruption that could induce abnormal migration characteristics seen in primordial germinal cells such as germinal premature failure or tumor invasion and metastasis. In conclusion, microsatellite instability could be a signal for primordial germinal cells pool selection, or tumorigenesis.