Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 2, 10

Progressive Obesity Leads to Altered Ovarian Gene Expression in the Lethal Yellow Mouse: A Microarray Study

Affiliations

Progressive Obesity Leads to Altered Ovarian Gene Expression in the Lethal Yellow Mouse: A Microarray Study

John Brannian et al. J Ovarian Res.

Abstract

Background: Lethal yellow (LY; C57BL/6J Ay/a) mice exhibit adult-onset obesity, altered metabolic regulation, and early reproductive senescence. The present study was designed to test the hypothesis that obese LY mice possess differences in expression of ovarian genes relative to age-matched lean mice.

Methods: 90- and 180-day-old LY and lean black (C57BL/6J a/a) mice were suppressed with GnRH antagonist (Antide(R)), then stimulated with 5 IU eCG. cRNA derived from RNA extracts of whole ovarian homogenates collected 36 h post-eCG were run individually on Codelink Mouse Whole Genome Bioarrays (GE Healthcare Life Sciences).

Results: Fifty-two genes showed >/= 2-fold differential (p < 0.05) expression between 180-day-old obese LY and lean black mice. LY mice 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 11beta-hydroxysteroid dehydrogenase type 1 (Hsd11b1) and a 2-fold lesser expression of 11beta-hydroxysteroid dehydrogenase type 2 (Hsd11b2), differences not seen in 90-day-old mice. Consistent with altered Hsd11b gene expression, ovarian concentrations of corticosterone (C) were elevated in aging LY mice relative to black mice, but C levels were similar in young LY and black mice.

Conclusion: The data suggest that reproductive dysfunction in aging obese mice is related to modified intraovarian gene expression that is directly related to acquired obesity.

Figures

Figure 1
Figure 1
Body weight (g) of 90 and 180-day black and LY mice (mean ± SEM; n = 3 for each group).
Figure 2
Figure 2
Genes (in bold type) involved in cholesterol biosynthesis exhibiting elevated expression (p < 0.05) in 180-day LY mice as compared to black mice. Numbers in boxes indicate fold difference (RU) in gene expression compared to black mice. Other genes in the pathway tended to be elevated (normal type with fold difference in parentheses).
Figure 3
Figure 3
Ovarian gene expression in 90- and 180-day LY mice relative to black mice analyzed by microarray (n = 3 for each group). Solid line indicates 1:1 expression ratio.
Figure 4
Figure 4
Ovarian expression of selected genes in 90- and 180-day LY and black mice analyzed by Real Time RT-PCR. Bars represent mean ratios (LY:black) of expression in 90- (black bars) and 180-day (gray bars) old mice. All samples were run in duplicate (n = 3 for each group).
Figure 5
Figure 5
Corticosterone concentrations in whole ovarian homogenates from 90- (black bars) and 180-day (gray bars) old black and LY mice. Bars represent mean ± SEM (n = 5 mice per group). Different letters denote statistical significance (P < 0.05) by ANOVA with Fisher's LSD test.

Similar articles

See all similar articles

Cited by 3 PubMed Central articles

References

    1. Wang JX, Davies M, Norman RJ. Body mass and probability of pregnancy during assisted reproduction treatment: retrospective study. Brit Med J. 2000;321:1320–1321. doi: 10.1136/bmj.321.7272.1320. - DOI - PMC - PubMed
    1. Norman RJ, Clark A. Obesity and reproductive disorders: a review. Reprod Fert Dev. 1998;10:55–63. doi: 10.1071/R98010. - DOI - PubMed
    1. Fedorcsák P, Storeng R, Dale PO, Tanbo T, Abyholm T. Obesity is a risk factor for early pregnancy loss after IVF or ICSI. Acta Obstet Gyn Scand. 2000;79:43–48. doi: 10.1034/j.1600-0412.2000.079001043.x. - DOI - PubMed
    1. Zhang Y, Proenca M, Maffei M, Barrone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature. 1994;372:425–432. doi: 10.1038/372425a0. - DOI - PubMed
    1. Tartaglia L, Dembski M, Weng X, et al. Identification and expression cloning of a leptin receptor, OB-R. Cell. 1995;83:1263–1271. doi: 10.1016/0092-8674(95)90151-5. - DOI - PubMed

LinkOut - more resources

Feedback