Alpha-Lipoic Acid Ameliorates Impaired Steroidogenesis in Human Granulosa Cells Induced by Advanced Glycation End-Products.

IF 1.6 Q2 MEDICINE, GENERAL & INTERNAL
Zahra Derakhshan, Soghra Bahmanpour, Mohammad Hossein Nasr-Esfahani, Fatemeh Masjedi, Maryam Mirani, Mahintaj Dara, Seyed Mohammad Bagher Tabei
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引用次数: 0

Abstract

Background: Ovarian granulosa cells (GCs) are essential for follicular development. Ovarian advanced glycation end-products (AGEs) accumulation is related to GCs dysfunction. Alpha-lipoic acid (ALA) illustrates therapeutic capabilities for infertility-related disorders. Therefore, this study assessed the effects of ALA on AGEs-induced GCs hormonal dysfunction.

Methods: The study was conducted from October 2021 to September 2022 at the Department of Medical Genetics, Shiraz University of Medical Sciences. Isolated GCs (n=50) were divided into control, human glycated albumin (HGA), HGA+ALA, and ALA treatments. Steroidogenic enzymes and AGE receptor (RAGE) genes were assessed by qRT-PCR. Steroid hormones and RAGE protein were evaluated using ELISA and Western blotting. Data were analyzed using GraphPad Prism software (ver. 9), and P<0.05 was considered significant.

Results: Our findings showed that HGA treatment significantly (P=0.0001) increased RAGE (by 140.66%), STAR (by 117.65%), 3β-HSD (by 165.68%), and 17β-HSD (by 122.15%) expression, while it decreased CYP19A1 (by 68.37%) expression. RAGE protein level (by 267.10%) was also increased in HGA-treated GCs. A significant decrease in estradiol (by 59.66%) and a slight and sharp elevation in progesterone (by 30.40%) and total testosterone (by 158.24%) levels was also observed. ALA treatment ameliorated the HGA-induced changes in steroidogenic enzyme mRNA levels (P=0.001) and steroid hormone secretion (P=0.010).

Conclusion: This work shows that ALA therapy likely corrects hormonal dysfunctions caused by AGEs in luteinized GCs. This effect is probably achieved by decreased RAGE expression. Clinical research is needed to understand how AGEs and ALA interact in the ovary, which might lead to a more targeted ovarian dysfunction therapy.

α-硫辛酸可改善高级糖化终产物诱导的人类颗粒细胞中受损的类固醇生成。
背景:卵巢颗粒细胞(GCs)对卵泡发育至关重要。卵巢高级糖化终产物(AGEs)的积累与 GCs 功能障碍有关。α-硫辛酸(ALA)具有治疗不孕症相关疾病的能力。因此,本研究评估了 ALA 对 AGEs 诱导的 GCs 激素功能障碍的影响:研究于 2021 年 10 月至 2022 年 9 月在设拉子医科大学医学遗传学系进行。分离的 GCs(n=50)分为对照组、人糖化白蛋白(HGA)组、HGA+ALA 组和 ALA 组。通过 qRT-PCR 评估类固醇生成酶和 AGE 受体(RAGE)基因。类固醇激素和 RAGE 蛋白通过 ELISA 和 Western 印迹法进行评估。使用 GraphPad Prism 软件(第 9 版)和 PResults 分析数据:我们的研究结果表明,HGA 能显著(P=0.0001)增加 RAGE(140.66%)、STAR(117.65%)、3β-HSD(165.68%)和 17β-HSD (122.15%)的表达,而降低 CYP19A1 (68.37%)的表达。经 HGA 处理的 GC 中,RAGE 蛋白水平也有所升高(267.10%)。此外,还观察到雌二醇水平明显下降(59.66%),孕酮(30.40%)和总睾酮(158.24%)水平略有急剧上升。ALA 治疗可改善 HGA 诱导的类固醇生成酶 mRNA 水平变化(P=0.001)和类固醇激素分泌变化(P=0.010):这项研究表明,ALA疗法可纠正黄体化GC中AGEs导致的激素功能障碍。这种效果可能是通过减少 RAGE 的表达实现的。临床研究需要了解 AGEs 和 ALA 在卵巢中是如何相互作用的,这可能会导致更有针对性的卵巢功能障碍疗法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Iranian Journal of Medical Sciences
Iranian Journal of Medical Sciences MEDICINE, GENERAL & INTERNAL-
CiteScore
3.20
自引率
0.00%
发文量
84
审稿时长
12 weeks
期刊介绍: The Iranian Journal of Medical Sciences (IJMS) is an international quarterly biomedical publication, which is sponsored by Shiraz University of Medical Sciences. The IJMS intends to provide a scientific medium of com­muni­cation for researchers throughout the globe. The journal welcomes original clinical articles as well as clinically oriented basic science re­search experiences on prevalent diseases in the region and analysis of various regional problems.
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