Zahra Derakhshan, Soghra Bahmanpour, Mohammad Hossein Nasr-Esfahani, Fatemeh Masjedi, Maryam Mirani, Mahintaj Dara, Seyed Mohammad Bagher Tabei
{"title":"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。","authors":"Zahra Derakhshan, Soghra Bahmanpour, Mohammad Hossein Nasr-Esfahani, Fatemeh Masjedi, Maryam Mirani, Mahintaj Dara, Seyed Mohammad Bagher Tabei","doi":"10.30476/IJMS.2023.99512.3168","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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 (<i>RAGE</i>) 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.</p><p><strong>Results: </strong>Our findings showed that HGA treatment significantly (P=0.0001) increased <i>RAGE</i> (by 140.66%), <i>STAR</i> (by 117.65%), <i>3β-HSD</i> (by 165.68%), and <i>17β-HSD</i> (by 122.15%) expression, while it decreased <i>CYP19A1</i> (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).</p><p><strong>Conclusion: </strong>This work shows that ALA therapy likely corrects hormonal dysfunctions caused by AGEs in luteinized GCs. This effect is probably achieved by decreased <i>RAGE</i> 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.</p>","PeriodicalId":14510,"journal":{"name":"Iranian Journal of Medical Sciences","volume":null,"pages":null},"PeriodicalIF":1.6000,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11347593/pdf/","citationCount":"0","resultStr":"{\"title\":\"Alpha-Lipoic Acid Ameliorates Impaired Steroidogenesis in Human Granulosa Cells Induced by Advanced Glycation End-Products.\",\"authors\":\"Zahra Derakhshan, Soghra Bahmanpour, Mohammad Hossein Nasr-Esfahani, Fatemeh Masjedi, Maryam Mirani, Mahintaj Dara, Seyed Mohammad Bagher Tabei\",\"doi\":\"10.30476/IJMS.2023.99512.3168\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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 (<i>RAGE</i>) 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.</p><p><strong>Results: </strong>Our findings showed that HGA treatment significantly (P=0.0001) increased <i>RAGE</i> (by 140.66%), <i>STAR</i> (by 117.65%), <i>3β-HSD</i> (by 165.68%), and <i>17β-HSD</i> (by 122.15%) expression, while it decreased <i>CYP19A1</i> (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).</p><p><strong>Conclusion: </strong>This work shows that ALA therapy likely corrects hormonal dysfunctions caused by AGEs in luteinized GCs. This effect is probably achieved by decreased <i>RAGE</i> 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.</p>\",\"PeriodicalId\":14510,\"journal\":{\"name\":\"Iranian Journal of Medical Sciences\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.6000,\"publicationDate\":\"2024-08-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11347593/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Iranian Journal of Medical Sciences\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.30476/IJMS.2023.99512.3168\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"MEDICINE, GENERAL & INTERNAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Iranian Journal of Medical Sciences","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.30476/IJMS.2023.99512.3168","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MEDICINE, GENERAL & INTERNAL","Score":null,"Total":0}
Alpha-Lipoic Acid Ameliorates Impaired Steroidogenesis in Human Granulosa Cells Induced by Advanced Glycation End-Products.
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.
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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