Department of Obstetrics & Gynecology, Sanford School of Medicine, University of South Dakota, Sioux Falls, SD 57105, USA.
J Ovarian Res. 2009 Aug 3;2:10. doi: 10.1186/1757-2215-2-10.
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.
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).
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.
The data suggest that reproductive dysfunction in aging obese mice is related to modified intraovarian gene expression that is directly related to acquired obesity.
致死性黄色（LY；C57BL/6J Ay/a）小鼠表现出成年期肥胖、代谢调节改变和早期生殖衰老。本研究旨在检验以下假设，即肥胖的 LY 小鼠与同龄瘦型小鼠相比，其卵巢基因的表达存在差异。
用 GnRH 拮抗剂（Antide（R））抑制 90 日龄和 180 日龄的 LY 和瘦型黑（C57BL/6J a/a）小鼠，然后用 5 IU eCG 刺激。eCG 后 36 小时收集的整个卵巢匀浆 RNA 提取物的 cRNA 分别在 Codelink Mouse Whole Genome Bioarrays（GE Healthcare Life Sciences）上运行。
180 日龄肥胖的 LY 和瘦型黑小鼠之间有 52 个基因的表达差异> 2 倍（p < 0.05）。LY 小鼠的卵巢中 agouti（350 倍）、瘦素（6.5 倍）和许多参与胆固醇/脂质转运和代谢的基因表达上调，如羊毛甾醇合酶、Cyp51 和类固醇急性调节蛋白（Star）。LY 小鼠中表达下调的基因较少，如血管紧张素原。相比之下，90 日龄肥胖的 LY 和黑小鼠体重相似，这些基因均无差异表达。有趣的是，180 日龄的 LY 小鼠 11β-羟甾脱氢酶 1 型（Hsd11b1）的表达增加了 2 倍，11β-羟甾脱氢酶 2 型（Hsd11b2）的表达减少了 2 倍，而 90 日龄的小鼠则没有这种变化。与 Hsd11b 基因表达改变一致，衰老 LY 小鼠的卵巢皮质酮（C）浓度相对于黑鼠升高，但年轻的 LY 和黑鼠的 C 水平相似。
数据表明，衰老肥胖小鼠的生殖功能障碍与获得性肥胖直接相关的卵巢内基因表达改变有关。
