Department of Pharmacology and Pharmacy PracticeK. B. Institute of Pharmaceutical Education and Research, Gandhinagar, Gujarat, India
Department of PharmacologyL. M. College of Pharmacy, Ahmedabad, Gujarat, India.
Reproduction. 2018 Feb;155(2):141-151. doi: 10.1530/REP-17-0584. Epub 2017 Dec 1.
Polycystic ovary syndrome (PCOS) is associated with hyperandrogenism, oligo-anovulation, polycystic ovaries and metabolic syndrome. Many researchers reported that PCOS often starts with menarche in adolescents. Presently available animal model focuses on ovarian but not metabolic features of PCOS. Therefore, we hypothesized that high-fat diet feeding to pre-pubertal female rats results in both reproductive and metabolic features of PCOS. Pre-pubertal female rats were divided into two groups: group I received normal pellet diet and group II received high-fat diet (HFD). In the letrozole study, adult female rats were divided into two groups: group I received 1% carboxy methyl cellulose and group II received 1 mg/kg letrozole orally. Oral glucose tolerance test, lipid profile, fasting glucose, insulin, estrus cycle, hormonal profile, ovary weight, luteinizing hormone (LH) receptor and follicle-stimulating hormone receptor expression were measured. Polycystic ovarian morphology was assessed through histopathological changes of ovary. Feeding of HFD gradually increase glucose intolerance and fasting insulin levels. Triglyceride level was higher in HFD study while total cholesterol level was higher in the letrozole study. Alteration in testosterone and estrogen levels was observed in both studies. LH receptor expression was upregulated only in HFD study. Histopathological changes like increase cystic follicle, diminished granulosa cell layer and thickened theca cell layer were observed in letrozole as well as HFD study. High-fat diet initiated at pre-puberty age in rats produces both metabolic disturbances and ovarian changes similar to that observed clinically in PCOS patients. Letrozole on the other hand induces change in ovarian structure and function.
多囊卵巢综合征（PCOS）与高雄激素血症、排卵障碍、多囊卵巢和代谢综合征有关。许多研究人员报告称，PCOS 通常始于青少年的初潮。目前现有的动物模型主要关注 PCOS 的卵巢而非代谢特征。因此，我们假设青春期前雌性大鼠的高脂肪饮食喂养会导致 PCOS 的生殖和代谢特征。青春期前雌性大鼠分为两组：第 I 组接受正常颗粒饮食，第 II 组接受高脂肪饮食（HFD）。在来曲唑研究中，成年雌性大鼠分为两组：第 I 组接受 1%羧甲基纤维素，第 II 组接受 1mg/kg 来曲唑口服。口服葡萄糖耐量试验、血脂谱、空腹血糖、胰岛素、发情周期、激素谱、卵巢重量、促黄体生成素（LH）受体和卵泡刺激素受体表达进行了测量。多囊卵巢形态通过卵巢的组织病理学变化进行评估。HFD 的喂养逐渐增加葡萄糖耐量和空腹胰岛素水平。HFD 研究中甘油三酯水平较高，而在来曲唑研究中总胆固醇水平较高。两种研究均观察到睾酮和雌激素水平的改变。仅在 HFD 研究中观察到 LH 受体表达上调。在来曲唑和 HFD 研究中均观察到囊性卵泡增加、颗粒细胞层减少和基膜细胞层增厚等组织病理学变化。青春期前大鼠的高脂肪饮食会导致代谢紊乱和卵巢变化，类似于临床观察到的 PCOS 患者。另一方面，来曲唑会导致卵巢结构和功能的改变。
