Fucoxanthin mitigates mercury-induced mitochondrial toxicity in the human ovarian granulosa cell line

Elmorsy, Ekramy M.; Al Doghaither, Huda A.; Al-Ghafari, Ayat B.; Amer, Saad; Fawzy, Manal S.; Toraih, Eman A.

Abstract

Mercury (Hg) is known to be a hazardous toxin with a significant negative impact on female reproduction through mechanisms that remain unclear. The carotenoid fucoxanthin (FX) is an antioxidant with several positive effects on human health. This study aimed to examine the potential protective role of FX in reducing the Hg-induced bioenergetic disturbances in a human ovarian granulosa cell line model. (methods briefly) Hg was found to reduce the viability of granulosa cells in a concentration-dependent manner, with an estimated 72-hour EC50 of 10 µM. In contrast, FX (10 and 20 µM) improved cell viability. Hg (1 and 10 µM) significantly reduced cellular ATP levels, mitochondrial membrane potential, oxygen consumption rates, and lactate production. Additionally, Hg impaired the activities and kinetics of mitochondrial complexes I and III and reduced the expression of mitochondrial genes ND1, ND5, cytochrome B, cytochrome C oxidase, and ATP synthase subunits 6 and 8. According to tests on mitochondrial membranes, Hg increased membrane fluidity by reducing saturated fatty acid levels and increasing those of unsaturated fatty acids. Hg also promoted mitochondrial swelling and enhanced the inner mitochondrial membrane permeability to hydrogen and potassium ions. FX (10 µM) was shown to mitigate the negative effects of Hg on the viability of treated granulosa cells, bioenergetics parameters, and mitochondrial membrane integrity in a concentration-dependent manner. Based on these findings, bioenergetic disruption may be a key underlying cause of Hg-induced ovarian dysfunction. Furthermore, FX may have a potential therapeutic role in treating ovarian disorders caused by Hg-induced disruption of granulosa cell bioenergetics.

Citation

Elmorsy, E. M., Al Doghaither, H. A., Al-Ghafari, A. B., Amer, S., Fawzy, M. S., & Toraih, E. A. (2025). Fucoxanthin mitigates mercury-induced mitochondrial toxicity in the human ovarian granulosa cell line. Reproductive Toxicology, 132, Article 108855. https://doi.org/10.1016/j.reprotox.2025.108855

• Journal Article Type: Article
• Acceptance Date: Feb 8, 2025
• Online Publication Date: Feb 11, 2025
• Publication Date: Mar 1, 2025
• Deposit Date: Feb 12, 2025
• Publicly Available Date: Feb 25, 2025
• Journal: Reproductive Toxicology
• Print ISSN: 0890-6238
• Electronic ISSN: 0890-6238
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 132
• Article Number: 108855
• DOI: https://doi.org/10.1016/j.reprotox.2025.108855
• Keywords: Fucoxanthin; Mercury; Granulosa cells; Mitochondria
• Public URL: https://nottingham-repository.worktribe.com/output/45309664
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S0890623825000267?via%3Dihub