Zhang Ting, Dai Pengyuan, Cheng Dong, Zhang Liang, Chen Zijiang, Meng Xiaoqian, Zhang Fumiao, Han Xiaoying, Liu Jianwei, Pan Jie, Yang Guiwen, Zhang Cong
Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Renji hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200135, China.
Reproduction. 2013 Dec 19;147(2):141-51. doi: 10.1530/REP-13-0470. Print 2014 Feb.
The Apolipoprotein (Apo) family is implicated in lipid metabolism. There are five types of Apo: Apoa, Apob, Apoc, Apod, and Apoe. Apoe has been demonstrated to play a central role in lipoprotein metabolism and to be essential for efficient receptor-mediated plasma clearance of chylomicron remnants and VLDL remnant particles by the liver. Apoe-deficient (Apoe(-/-)) mice develop atherosclerotic plaques spontaneously, followed by obesity. In this study, we investigated whether lipid deposition caused by Apoe knockout affects reproduction in female mice. The results demonstrated that Apoe(-/-) mice were severely hypercholesterolemic, with their cholesterol metabolism disordered, and lipid accumulating in the ovaries causing the ovaries to be heavier compared with the WT counterparts. In addition, estrogen and progesterone decreased significantly at D 100. Quantitative PCR analysis demonstrated that at D 100 the expression of cytochromeP450 aromatase (Cyp19a1), 3β-hydroxysteroid dehydrogenase (Hsd3b), mechanistic target of rapamycin (Mtor), and nuclear factor-κB (Nfkb) decreased significantly, while that of BCL2-associated agonist of cell death (Bad) and tuberous sclerosis complex 2 (Tsc2) increased significantly in the Apoe(-/-) mice. However, there was no difference in the fertility rates of the Apoe(-/-) and WT mice; that is, obesity induced by Apoe knockout has no significant effect on reproduction. However, the deletion of Apoe increased the number of ovarian follicles and the ratio of ovarian follicle atresia and apoptosis. We believe that this work will augment our understanding of the role of Apoe in reproduction.
载脂蛋白（Apo）家族与脂质代谢有关。Apo有五种类型：Apoa、Apob、Apoc、Apod和Apoe。已证明Apoe在脂蛋白代谢中起核心作用，并且对于肝脏通过受体介导有效清除乳糜微粒残余物和极低密度脂蛋白（VLDL）残余颗粒至关重要。载脂蛋白E缺陷（Apoe(-/-)）小鼠会自发形成动脉粥样硬化斑块，随后出现肥胖。在本研究中，我们调查了Apoe基因敲除引起的脂质沉积是否会影响雌性小鼠的繁殖。结果表明，Apoe(-/-)小鼠严重高胆固醇血症，其胆固醇代谢紊乱，脂质在卵巢中蓄积，导致卵巢比野生型对照更重。此外，在第100天时雌激素和孕酮显著降低。定量PCR分析表明，在第100天时，Apoe(-/-)小鼠中细胞色素P450芳香化酶（Cyp19a1）、3β-羟基类固醇脱氢酶（Hsd3b）、雷帕霉素作用靶点（Mtor）和核因子κB（Nfkb）的表达显著降低，而细胞死亡相关的BCL2激动剂（Bad）和结节性硬化复合物2（Tsc2）的表达显著增加。然而，Apoe(-/-)小鼠和野生型小鼠的生育率没有差异；也就是说，Apoe基因敲除诱导的肥胖对繁殖没有显著影响。然而，Apoe的缺失增加了卵巢卵泡数量以及卵巢卵泡闭锁和凋亡的比例。我们相信这项工作将增进我们对Apoe在生殖中的作用的理解。
