Altered ovarian gene expression in the lethal yellow mouse

ABSTRACT: Mice possessing the lethal yellow (LY) agouti mutation (C57BL/6J Ay/a) exhibit adult-onset obesity, altered metabolic regulation, and early reproductive senescence. The present study was designed to test the hypothesis that aging obese mice possess differences in expression of ovarian genes involved in reproductive function relative to age-matched lean mice. To synchronize ovarian state and exclude gonadotropin-mediated effects, 90- and 180-day old diestrous LY and lean black (C57BL/6J a/a) mice were suppressed with GnRH antagonist (Antide®) for five days, then injected with 5 IU equine chorionic gonadotropin (eCG). Complementary RNA derived from RNA extracts of whole ovarian homogenates collected 36h post eCG were run individually on CodeLink Mouse Whole Genome Bioarrays (Applied Microarrays). Unidentified genes, EST, genes whose expression was below sensitivity limits, and those with less than a 2-fold difference in expression between groups were excluded from analysis. After exclusions, 52 genes had a significant (p<0.05) difference in expression between 180-day-old obese LY and lean black mice. LY exhibited elevated ovarian expression of agouti (350x), leptin (6.5x), and numerous genes involved in cholesterol/lipid transport and metabolism, e.g., lanosterol synthase, CYP51, and steroidogenic acute regulatory protein (StAR). Fewer genes showed lower expression in LY mice, e.g. angiotensinogen. In contrast, none of these genes showed differential expression in 90-day-old LY and black mice, which are of similar body weight. Interestingly, 180-day-old LY mice had a 2-fold greater expression of 11β-hydroxysteroid dehydrogenase (HSD) type 1 and a 2-fold lesser expression of 11β-HSD type 2, differences not seen in 90-day-old mice. Consistent with altered 11β-HSD expression, ovarian concentrations of corticosterone (C) were elevated in aging (180-day) LY mice relative to black mice, but C levels were similar in young (90-day) LY and black mice. The data suggest that reproductive dysfunction in aging obese mice is related to modified intraovarian gene expression that is directly related to acquired obesity, but independent of gonadotropic state.

ORGANISM(S): Mus musculus

PROVIDER: GSE14937 | GEO | 2010/02/18

SECONDARY ACCESSION(S): PRJNA111979

REPOSITORIES: GEO