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多囊卵巢综合征产前雄激素化大鼠模型成年后葡萄糖耐量受损及胰岛素抵抗

Impaired glucose tolerance and insulin resistance in a prenatally-androgenized rat model of polycystic ovary syndrome in later life.

作者信息

Farhadi-Azar Mahbanoo, Noroozzadeh Mahsa, Mousavi Maryam, Saei Ghare Naz Marzieh, Ramezani Tehrani Fahimeh

机构信息

Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Foundation for Research & Education Excellence, Vestavia Hills, AL, USA.

出版信息

Exp Physiol. 2025 Mar;110(3):410-423. doi: 10.1113/EP091912. Epub 2024 Nov 29.

Abstract

Polycystic ovary syndrome (PCOS), one of the most common endocrine disorders in reproductive-aged women, is associated with metabolic disturbances. The present study aimed to examine changes in body weight (BW) and glucose and insulin tolerance in a prenatally-androgenized (PNA) rat model of PCOS compared to control with increasing age. Pregnant rats in the experimental group were subcutaneously injected with 5 mg of free testosterone on the 20th day of pregnancy, while the control group received the solvent. Female offspring of both groups, PNA rats (rat model of PCOS) and control, were examined in terms of changes in BW, glucose and insulin tolerance at 3, 6, 12 and 20 months of age. BW at birth (6.53 ± 0.89 vs. 5.60 ± 1.18 g; P = 0.038), 15 (25 ± 1.15 vs. 22.36 ± 3.98 g; P = 0.019) and 30 (59.37 ± 10.19 vs.49.9 ± 9.39 g; P = 0.022) days of age was significantly increased in the rat model of PCOS compared to control, but no significant differences were observed in BW of the rat model of PCOS compared to control at 60 (P = 0.155) and 75 (P = 0.932) days or at 3 (P = 0.239), 6 (P = 0.782), 12 (P = 0.755) and 20 (P = 0.092) months of age. Rat model of PCOS showed impaired glucose tolerance (IGT) at 3 months of age (P = 0.020) and insulin resistance (IR) with increasing age (3-20 months of age) compared to control. Increased BW before puberty, IGT at 3 months of age and IR with increasing age were observed in our rat model of PCOS. This rat model may contribute to a better understanding of underlying mechanisms of changes in BW, IGT and IR in future studies.

摘要

多囊卵巢综合征(PCOS)是育龄女性中最常见的内分泌紊乱疾病之一,与代谢紊乱有关。本研究旨在探讨与对照组相比,多囊卵巢综合征产前雄激素化(PNA)大鼠模型随着年龄增长体重(BW)、葡萄糖耐量和胰岛素耐量的变化。实验组的怀孕大鼠在妊娠第20天皮下注射5毫克游离睾酮,而对照组注射溶剂。对两组的雌性后代,即PNA大鼠(多囊卵巢综合征大鼠模型)和对照组,在3、6、12和20月龄时进行BW、葡萄糖耐量和胰岛素耐量变化的检测。与对照组相比,多囊卵巢综合征大鼠模型出生时(6.53±0.89对5.60±1.18克;P = 0.038)、15日龄(25±1.15对22.36±3.98克;P = 0.019)和30日龄(59.37±10.19对49.9±9.39克;P = 0.022)的BW显著增加,但在60日龄(P = 0.155)和75日龄(P = 0.932)或3月龄(P = 0.239)、6月龄(P = 0.782)、12月龄(P = 0.755)和20月龄(P = 0.09)时,多囊卵巢综合征大鼠模型与对照组的BW无显著差异。与对照组相比,多囊卵巢综合征大鼠模型在3月龄时出现葡萄糖耐量受损(IGT)(P = 0.020),且随着年龄增长(3至20月龄)出现胰岛素抵抗(IR)。在我们的多囊卵巢综合征大鼠模型中,观察到青春期前BW增加、3月龄时IGT以及随着年龄增长出现IR。该大鼠模型可能有助于在未来研究中更好地理解BW、IGT和IR变化的潜在机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3531/11868029/cbe067f9bed5/EPH-110-410-g006.jpg

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