Abstract
Endometriosis is a chronic, multifactorial disorder. Reactive oxygen species (ROS) and oxidative stress (OS) contribute to the development of endometriosis by affecting apoptosis-related genes in granulosa cells. N-acetylcysteine (NAC) is an antioxidant that reduces OS. This randomized controlled trial aimed to investigate the effects of NAC on serum levels of superoxide dismutase (SOD) and total antioxidant capacity (TAC), as well as the expression of apoptotic genes in granulosa cells. Infertile women with endometriosis were enrolled and administered either NAC (1200 mg/day; n = 11) or placebo (n = 14). Enzyme-linked immunosorbent assay (ELISA) was used to measure serum SOD and TAC levels. The expression of Bcl-2, Bax, and Caspase-3 genes in granulosa cells was evaluated by Real-Time Polymerase Chain Reaction. NAC treatment increased serum SOD and TAC levels. Additionally, the expression of pro-apoptotic genes Bax and Caspase-3 in granulosa cells decreased compared to the placebo group, while the expression of the anti-apoptotic gene Bcl-2 increased. We conclude that administration of N-acetylcysteine (NAC) can reduce apoptosis in granulosa cells of women with infertility due to endometriosis.
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The archived datasets analyzed in support of the conclusions of this article (raw qPCR and ELISA data) will be made available upon logical request by the first or corresponding authors.
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Acknowledgements
This study was financially sponsored by the Genetic department of Royan Institute, Tehran, Iran and Royan Lotus Charity Foundation. The authors dedicate this article to the memory of Dr. Saeid Kazemi Ashtiani, the late founder of Royan Institute.
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The funding of this project was provided by the Genetics Department of Royan Institute.
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ZSH, PA, MH, Contributed to conception and design; ZSH, Contributed to all experimental work, data and statistical analysis, and interpretation of data; PA, MH, Were responsible for overall supervision; MKHF, PEY,AM Cooperated in the sampling section; MH, Was responsible for patients assessment and diagnosis, also for patient recruitment to study; ZSH, Collected the samples; ZSH, Calculated the number of samples; FA, Cooperated with some experimental tests; ZSH analyzed the row data; AAY, helped with interpretation of results; ZSH, Drafted the initial manuscript and wrote the manuscript; PA, AAY, Contributed to revise and edit the manuscript; All authors read and approved the final manuscript.
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The study was conducted in accordance with the Declaration of Helsinki, and approved by the Research Ethics Committee of the Royan Institute (Code No.: IR.ACECR.ROYAN.REC.1398.111).
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Heshmati, Z.S., Amiri-Yekta, A., Khosravifar, M. et al. Administration of N-acetylcysteine influence the expression of apoptotic genes in the granulosa cells of infertile women diagnosed with endometriosis. Sci Rep (2026). https://doi.org/10.1038/s41598-025-34202-0
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DOI: https://doi.org/10.1038/s41598-025-34202-0


