Protective effect of resveratrol against ovarian dysfunction in endometriotic rats
DOI:
https://doi.org/10.30539/1evm3f65Keywords:
Endometriosis, Resveratrol, Estrogen Signaling, Inflammatory Response, Ovarian FunctionAbstract
Background: Endometriosis (END) is an estrogen-dependent inflammatory disorder associated with pelvic pain, infertility, and ovarian dysfunction. Till today, there is no cure for END, only attempts to alleviate its symptoms. Resveratrol (RES), a natural polyphenolic compound, has revealed anti-inflammatory and anti-estrogenic effects, indicating its potential as a novel beneficial agent. This study aimed to assess the protective impacts of RES on ovarian function and the progression of END in a rat model, concentrating on estrogen signaling, immune-inflammatory responses, coagulation abnormalities, and histological alterations. Methodology: END was induced in adult female rats via endometrial tissue transplants harvested from donor rats. Endometriotic rats were divided into untreated (END), vehicle-treated (END+DMSO), and RES-treated (END+RES). Serum and peritoneal exudate of estradiol (E2) levels, percentage of granulocyte cells and Mid cells (monocytes, eosinophils, basophils), coagulation markers (platelet counts, fibrinogen, thrombin time, and prothrombin time), and ovarian histopathology were assessed. Results: Analyzed data showed that END and END+DMSO rats had elevated E2 levels, increased granulocyte and Mid cell percentages, a hypercoagulable state, and significant ovarian tissue alterations. However, RES administration to the endometriotic group reversed the deleterious alterations and improved the ovarian architecture. Conclusions: Altogether, this study can conclude that RES alleviated significant pathogenic features of END via hormonal, immunological, and coagulative regulation, while protecting ovarian function.
Downloads
References
Abdulla, J. M. & Al-Okaily, B. N.(2022). Histomorphometric and histopathological alterations of rat testis following exposure to hydrogen peroxide: Protective role of resveratrol supplement. The Iraqi Journal of Veterinary Medicine, 46 (1), 17-23. https://doi.org/10.30539/ijvm.v46i1.1313
Adilbayeva, A. & Kunz, J.(2024). Pathogenesis of endometriosis and endometriosis-associated cancers. International Journal of Molecular Sciences, 25 (14), 7624. https://doi.org/10.3390/ijms25147624
Agarwal, S. K., Chapron, C., Giudice, L. C., Laufer, M. R., Leyland, N., Missmer, S. A., Singh, S. S. & Taylor, H. S.(2019). Clinical diagnosis of endometriosis: a call to action. American Journal of Obstetrics and Gynecology, 220 (4), 354.e1-354.e12. https://doi.org/10.1016/j.ajog.2018.12.039
Aghetaa, H. F. K., Dawood, R. A. & Aladhami, A. K.(2023). Resveratrol administration ameliorates hepatotoxicity in mercuric chloride-induced liver injury in Rats. The Iraqi Journal of Veterinary Medicine, 47 (2), 1-8. https://doi.org/10.30539/ijvm.v47i2.1482
Ahmed, R. M. & Mohammed, A. K.(2022). Role of sodium butyrate supplement on reducing hepatotoxicity induced by lead acetate in rats. The Iraqi Journal of Veterinary Medicine, 46 (2), 29-35. https://doi.org/10.30539/ijvm.v46i2.1408
Al-Hassawi, W. W. & Al-Sammak, M. A.(2024). Resveratrol as an antiaging drug: A Review of articles. Iraqi Journal of Pharmaceutical Sciences, 33 (2), 1-13. https://doi.org/10.31351/vol33iss3pp1-13
Al-Khaqani, B. A. & Mohammad, A. K. (2024). The therapeutic responses of resveratrol against ovalbumin-induced asthma influenced via upregulation of forkhead box transcription factor in rats. Iraqi Journal of Biotechnology, 23 (3), 185-193.
Al-Salamy, A. A. & Alghetaa, H. (2025). Resveratrol administration reverses the endometriosis-mediated outcomes via Tgfβ signaling in rats. Journal of Animal Health and Production, 13(4), 983. https://doi.org/10.17582/journal.jahp/2025/13.4.983.1001
Alawady, E. Y. & Alrubeii, A.(2024). The role of the resveratrol as antioxidant in improving the chemical and qualitative properties of chilled ground beef. Iraqi Journal of Agricultural Sciences, 55 (6), 1994-2005. https://doi.org/10.36103/s7dat782
Alghetaa, H., Mohammed, A., Singh, N. P., Bloomquist, R. F., Chatzistamou, I., Nagarkatti, M. & Nagarkatti, P.(2023). Estrobolome dysregulation is associated with altered immunometabolism in a mouse model of endometriosis. Frontiers in Endocrinology, 14. https://doi.org/10.3389/fendo.2023.1261781
Alharris, E., Mohammed, A., Alghetaa, H., Zhou, J., Nagarkatti, M. & Nagarkatti, P. (2022). The ability of resveratrol to attenuate ovalbumin-mediated allergic asthma is associated with changes in microbiota involving the gut-lung axis, enhanced barrier function and decreased inflammation in the lungs. Frontiers in Immunology, 13. https://doi.org/10.3389/fimmu.2022.805770
Alharris, E. S., Alghetaa, H. F., Busbee, P. B., Nagarkatti, M. & Nagarkatti, P.(2018). Resveratrol treatment alters lung microbiome in the murine ovalbumin-induced asthma model by increasing mucus-degrading Akkermansia muciniphila. The Journal of Immunology, 200 (Supplement_1), 44.31-44.31. https://doi.org/10.4049/jimmunol.200.Supp.44.31
Angellotti, G., Di Prima, G., Belfiore, E., Campisi, G. & De Caro, V.(2023). Chemopreventive and anticancer role of resveratrol against oral squamous cell carcinoma. Pharmaceutics, 15 (1), 275. https://doi.org/10.3390/pharmaceutics15010275
Aziz, H., Malik, J., Ahmad, S., Eusaph, A. Z., Iqbal, M. A. & Roohi, N.(2023). Fibrinogen, a biomarker for early diagnosis of endometriosis. Journal of Biological Regulator and Homeostatic Agents, 37 (1), 141-50. https://doi.org/10.23812/j.biol.regul.homeost.agents.20233701.14
Bustani, G., Al-Humadi, N. & Alghetaa, H.(2024). Aryl hydrocarbon receptor modulation and resveratrol influence on Dnah1 expression: implications for male reproductive health. The Iraqi Journal of Veterinary Medicine, 48 (1), 15-24. https://doi.org/10.30539/p5wv8002
Bustani, G. S. & Alghetaa, H. F. K.(2025). Aryl hydrocarbon receptor signaling in male fertility: Protective role of resveratrol and disruptive effects of CH223191 in adult male rats. Veterinary World, 18 (5), 1274. https://doi.org/10.14202/vetworld.2025.1274-1287
Calmon, M. S., Lemos, F. F. B., Luz, M. S., Pinheiro, S. L. R., De Oliveira Silva, L. G., Santos, G. L. C., Rocha, G. R. & De Melo, F. F.(2024). Immune pathway through endometriosis to ovarian cancer. World Journal of Clinical Oncology, 15 (4), 496. https://doi.org/10.5306/wjco.v15.i4.496
Chantalat, E., Valera, M.-C., Vaysse, C., Noirrit, E., Rusidze, M., Weyl, A., Vergriete, K., Buscail, E., Lluel, P. & Fontaine, C.(2020). Estrogen receptors and endometriosis. International Journal of Molecular Sciences, 21 (8), 2815. https://doi.org/10.3390/ijms21082815
Chauhan, S., Jarpula, D., Krishna, K. V., Bali, S. & Shah, U.(2025). Resveratrol and tumorigenesis: advanced computational and biochemical approaches to understanding its anticancer mechanisms. Plant-Based Cancer Fighters: The Molecular Science and Therapeutic Potential of Herbal Remedies in Oncology.
Dash, S. P., Gupta, S. & Sarangi, P. P.(2024). Monocytes and macrophages: Origin, homing, differentiation, and functionality during inflammation. Heliyon, 10 (8), 10. https://doi.org/10.1016/j.heliyon.2024.e29686
Ding, S., Lin, Q., Zhu, T., Li, T., Zhu, L., Wang, J. & Zhang, X.(2019). Is there a correlation between inflammatory markers and coagulation parameters in women with advanced ovarian endometriosis? BMC Women's Health, 19 (1), 169. https://doi.org/10.1186/s12905-019-0860-9
Gal, R., Deres, L., Toth, K., Halmosi, R. & Habon, T.(2021). The effect of resveratrol on the cardiovascular system from molecular mechanisms to clinical results. International Journal of Molecular Sciences, 22 (18), 10152. https://doi.org/10.3390/ijms221810152
Greygoose, E., Metharom, P., Kula, H., Seckin, T. K., Seckin, T. A., Ayhan, A. & Yu, Y.(2025). The estrogen–immune interface in endometriosis. Cells, 14 (1). https://doi.org/10.3390/cells14010058
Han, S., Cicek, A. F., Tokmak, A., Yildirir Ustun, T., Ercan Gokay, N., Uludag, M. O. & Demirel, M. A.(2021). Effects of resveratrol on receptor expression and serum levels of estrogen and progesterone in the rat endometritis model. Reproductive Sciences, 28 (9), 2610-2622. https://doi.org/10.1007/s43032-021-00586-3
Jasim, R. Z. & Yaseen, S. M. (2024). The biochemical role of environmental pollution in the etiology of endometriosis. Journals Kufa for Chamical, 4 (1). https://doi.org/10.36329/jkcm/2024/v4.i1.14821
Khayoon, H. A. & Al-Rekabi, F. M. K.(2020). Cytotoxic effect of resveratrol on colorectal cancer cell line. The Iraqi Journal of Veterinary Medicine, 44 (1), 68-74. https://doi.org/10.30539/ijvm.v44i1.939
Khazaei, M. R., Rashidi, Z., Chobsaz, F., Niromand, E. & Khazaei, M.(2020). Inhibitory effect of resveratrol on the growth and angiogenesis of human endometrial tissue in an in vitro three-dimensional model of endometriosis. Reproductive Biology, 20 (4), 484-490. https://doi.org/10.1016/j.repbio.2020.07.012
Lamceva, J., Uljanovs, R. & Strumfa, I.(2023). The main theories on the pathogenesis of endometriosis. International Journal of Molecular Sciences, 24 (5). https://doi.org/10.3390/ijms24054254
Mariadas, H., Chen, J. H. & Chen, K. H.(2025). The molecular and cellular mechanisms of endometriosis: from basic pathophysiology to clinical implications. International Journal of Molecular Sciences, 26 (6), 2458. https://doi.org/10.3390/ijms26062458
Nannini, G., Cei, F. & Amedei, A.(2025). Unraveling the contribution of estrobolome alterations to endometriosis pathogenesis. Current Issues in Molecular Biology, 47 (7), 502. https://doi.org/10.3390/cimb47070502
Neykhonji, M., Al-Asady, A. M., Al Okla, S., Al-Nazwani, N., Avan, A., Khazaei, M. & Hassanian, S. M.(2025). Phytoestrogens: a promising therapeutic approach for endometriosis management, insights from preclinical and clinical studies. Current Pharmaceutical Design. https://doi.org/10.2174/0113816128364775250326161410
Othman, E. R., Markeb, A. A., Khashbah, M. Y., Abdelaal, I. I., Elmelegy, T. T., Fetih, A. N., Van Der Houwen, L. E., Lambalk, C. B. & Mijatovic, V. (2021). Markers of local and systemic estrogen metabolism in endometriosis. Reproductive Sciences, 28 (4), 1001-1011. https://doi.org/10.1007/s43032-020-00383-4
Parmar, G., Howard, A. F., Noga, H., Tannock, L., Abdulai, A.-F., Allaire, C., Lett, S., Sutherland, J., De Arbina, E. L. & Hummelshoj, L.(2025). Pelvic pain & endometriosis: the development of a patient-centred e-health resource for those affected by endometriosis-associated dyspareunia. BMC Medical Informatics & Decision Making, 25 79. https://doi.org/10.1186/s12911-025-02907-x
Peng, Y., Xiong, W., He, H., Liu, H., Fu, T., Long, X., Li, X., Dai, X., Xu, Y., Zhang, L. & Liu, Y.(2025). Estradiol promotes endometriosis progression via the ERβ/QKI /circSMAD2 axis. Current Pharmaceutical Biotechnology, 26. https://doi.org/10.2174/0113892010331129250216041033
Wang, D., Geng, M., Gan, D., Han, G., Gao, G., Xing, A., Cui, Y. & Hu, Y.(2021). Effect of resveratrol on mouse ovarian vitrification and transplantation. Reproductive Biology & Endocrinology, 19 (1), 54. https://doi.org/10.1186/s12958-021-00735-y
Yu, Z., Zhu, W., Lu, F., Liu, H., Sun, H., Dong, J., Zhang, Y. & Wang, H.(2024). Inhibitory effects of resveratrol on platelet activation and thrombosis in colon cancer through regulation of the MAPK and cGMP/VASP pathways. Thrombosis Research, 241 109111. https://doi.org/10.1016/j.thromres.2024.109111
Zaurito, A., Mehmeti, I., Limongelli, F., Zupo, R., Annunziato, A., Fontana, S. & Tardugno, R.(2024). Natural compounds for endometriosis and related chronic pelvic pain: A review. Fitoterapia, 179. https://doi.org/10.1016/j.fitote.2024.106277
Downloads
Published
Issue
Section
License
Copyright (c) 2025 Experimental and Applied Veterinary Research Journal
This work is licensed under a Creative Commons Attribution 4.0 International License.
