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

Document Type : Original Article(s)

Authors

1 Department of Reproductive Biology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran

2 Department of Anatomy and Reproductive Biology, School of Medical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran

3 Department of Animal Biotechnology, Reproductive Biomedicine Research Center, Royan Institute for Biotechnology, Isfahan, Iran

4 Isfahan Fertility and Infertility Center, Isfahan, Iran

5 Shiraz Nephro-Urology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

6 Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

7 Department of Medical Genetics, School of Medical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran

8 Maternal-fetal Medicine Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

10.30476/ijms.2023.99512.3168

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.

Keywords

References
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Iranian Journal of Medical Sciences

Articles InPress, Corrected Proof
Available Online from 27 December 2023
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  • Received: 26 July 2023
  • Revised: 08 November 2023
  • Accepted: 20 October 2023
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