International Journal of Reproductive BioMedicine

Published date: Feb 24 2025

Journal Title: International Journal of Reproductive BioMedicine

Issue title: International Journal of Reproductive BioMedicine (IJRM): Volume 23, Issue No. 1

Pages: 79 - 90

DOI: 10.18502/ijrm.v23i1.18201

Ensiyeh Mohebbi KianDepartment of Pharmacy, Ayatollah Amoli Branch, Islamic Azad University, Amol

Maryam BarancheshmehDepartment of Pharmacy, Ayatollah Amoli Branch, Islamic Azad University, Amol

Hossein Najafzadehvarzih.najafzadeh@mubabol.ac.irPharmacology Department, Faculty of Medicine, Babol University of Medical Sciences, Babol

Seyedeh Masoumeh GhoreishiCellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol

Naser ShokrzadehReproductive Health Research Center, Clinical Research Institute, Urmia University of Medical Sciences, Urmia

Background: Polycystic ovarian syndrome (PCOS) is a prevalent hormonal disorder among women of reproductive age, resulting in female infertility. Researchers are exploring safe and affordable treatments for this disorder.

Objective: This study explored the therapeutic effects of fennel essential oil (FEO) and manganese (Mn) on hormonal and histological markers in rats with estradiol valerate-induced PCOS.

Materials and Methods: In this experimental study, 35 adult female Wistar rats (9 wk old, 200–250 gr) were divided into 7 groups. For 14 days, groups 1–4 received normal saline intraperitoneally, sesame oil intramuscularly, FEO intraperitoneally, and Mn orally, respectively. PCOS was induced in remaining groups through a single intramuscular injection of estradiol valerate. 60 days after induction, the 6th and 7th groups were treated individually with intraperitoneal FEO and oral Mn for 14 days. Blood samples were analyzed for estrogen, progesterone, and malondialdehyde (MDA) markers. The ovarian tissues were histologically examined to assess cyst formation and structural changes.

Results: FEO significantly increased estrogen and progesterone levels in PCOS rats compared to the PCOS group (p ≤ 0.05). Mn also elevated progesterone levels, but the change was not statistically significant (p > 0.05). No significant differences in MDA levels were observed between the PCOS and PCOS+FEO groups. Although MDA levels decreased in the PCOS+Mn group, the reduction was not statistically significant (p > 0.05). Both FEO and Mn treatments significantly reduced ovarian cyst numbers compared to untreated PCOS rats (p ≤ 0.05).

Conclusion: FEO and Mn demonstrated potential in restoring hormonal balance and improving ovarian histology, offering promise as low-cost treatments for PCOS.

Keywords: PCOS, Rat, FEO, Mn, Oxidative stress, Estrogen, Progesterone

[1] Teede HJ, Misso ML, Costello MF, Dokras A, Laven J, Moran L, et al. Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome. Fertil Steril 2018; 110: 364–379.

[2] Hoeger KM, Dokras A, Piltonen T. Update on PCOS: Consequences, challenges, and guiding treatment. J Clin Endocrinol Metab 2021; 106: e1071–1083.

[3] Hajam YA, Rather HA, Neelam, Kumar R, Basheer M, Reshi MS. A review on critical appraisal and pathogenesis of polycystic ovarian syndrome. Endocr Metab Sci 2024; 14: 100162.

[4] Patel S. Polycystic ovary syndrome (PCOS), an inflammatory, systemic, lifestyle endocrinopathy. J Steroid Biochem Mol Biol 2018; 182: 27–36.

[5] Briden L, Shirin S, Prior JC. The central role of ovulatory disturbances in the etiology of androgenic polycystic ovary syndrome (PCOS): Evidence for treatment with cyclic progesterone. Drug Discov Today Dis Model 2020; 32: 71–82.

[6] Kuryłowicz A. Adipose tissue as a cause of endocrine dysfunction. Endokrynol Pol 2023; 74: 468–479.

[7] Mohammadi M. Oxidative stress and polycystic ovary syndrome: A brief review. Int J Prev Med 2019; 10: 86.

[8] Escobar-Morreale HF. Polycystic ovary syndrome: Definition, aetiology, diagnosis and treatment. Nat Rev Endocrinol 2018; 14: 270–284.

[9] Shamalizade Baii F, Barancheshme M, Bakhshi Jouybari H, Habibi E. Traditional uses, chemistry and pharmacology of Ruscus genus (“Murd esfarm” in traditional Persian medicine): A review. Res J Pharmacogn 2017; 4 (Suppl.): 47.

[10] Chaudary AS, Guo Y, Utkin YN, Barancheshmeh M, Dagda RK, Gasanoff ES. Sphingomyelin inhibits hydrolytic activity of heterodimeric PLA2 in model myelin membranes: Pharmacological relevance. J Membr Biol 2024; 258: 29–46.

[11] Barancheshmeh M, Najafzadehvarzi H, Shokrzadeh N, Aram C. Comparative analysis of fennel essential oil and manganese in PCOS rat model via modulating miR-145 expression and structure-based virtual screening of IGF2R protein to address insulin resistance and obesity. Obes Med 2025; 53: 100574.

[12] Li L, Yang X. The essential element manganese, oxidative stress, and metabolic diseases: Links and interactions. Oxid Med Cell Longev 2018; 2018: 7580707.

[13] Studer JM, Schweer WP, Gabler NK, Ross JW. Functions of manganese in reproduction. Anim Reprod Sci 2022; 238: 106924.

[14] Moradi Negahdari F, Hadjadeh M, Gholamnezhad Z, Sohrabi F, Samadi Noshahr Z. The protective effects of trans-anethole against polycystic ovary syndrome induced histopathological and metabolic changes in rat. Int J Fertil Steril 2022; 16: 192.

[15] Gunkov S, Tatarchuk T, Zhminko P, Regeda S. [Effect of manganese and nickel on prolactin levels in women with polycystic ovary syndrome]. Georgian Med News 2019; 289: 21–25. (in Russian)

[16] Mehra N, Tamta G, Nand V. A review on nutritional value, phytochemical and pharmacological attributes of Foeniculum vulgare mill. J Pharmacogn Phytochem 2021; 10: 1255–1263.

[17] Sadeghpour N, Khaki AA, Najafpour A, Dolatkhah H, Montaseri A. Study of Foeniculum vulgare (fennel) seed extract effects on serum level of estrogen, progesterone and prolactin in mouse. Crescent J Med Biol Sci 2015; 2: 23–27.

[18] Meena M, Sharma M, Dhakar A, Singh C, Sharma L, Purvia RP. Role of Foeniculum vulgare in PCOS: A review article. World J Pharm Res 2019; 8: 344–350.

[19] Zeng LH, Rana S, Hussain L, Asif M, Mehmood MH, Imran I, et al. Polycystic ovary syndrome: A disorder of reproductive age, its pathogenesis, and a discussion on the emerging role of herbal remedies. Front Pharmacol 2022; 13: 874914.

[20] Aguilar Diaz De Leon J, Borges CR. Evaluation of oxidative stress in biological samples using the thiobarbituric acid reactive substances assay. J Vis Exp 2020; 159: 10.3791.

[21] Chandran A, Merlin JN, Ammu L, Dharan SS. Fennel treatment to PCOS: An insilico evaluation to explore the therapeutic efficacy of anethole. Res J Pharm Technol 2019; 12: 4958–4962.

[22] Alivandi Farkhad S, Khazali H. Therapeutic effects of isoflavone-aglycone fraction from soybean (Glycine max L. Merrill) in rats with estradiol valerate-induced polycystic ovary syndrome as an inflammatory state. Gynecol Endocrinol 2019; 35: 1078–1083.

[23] Naji M, Nekoonam S, Aleyasin A, Arefian E, Mahdian R, Azizi E, et al. Expression of miR-15a, miR-145, and miR-182 in granulosa-lutein cells, follicular fluid, and serum of women with polycystic ovary syndrome (PCOS). Arch Gynecol Obstet 2018; 297: 221–231.

[24] Seif Amirhoseiny E, Ganji A, Mosayebi G, Ghazavi A. [Immunomodulatory effect of fennel in animal model of polycystic ovarian syndrome]. J Arak Univ Med Sci 2020; 23: 22–33. (in Persian)

[25] Khosrowpour Z, Fahimi S, Faizi M, Shaaban Z, Tansaz M, Sahranavard S. Evaluation of formulated herbal syrup (containing fennel, anise, and celery) on the letrozole-induced polycystic ovary syndrome model. Jundishapur J Nat Pharm Prod 2022; 17: e120814.

[26] Desmawati D, Sulastri D. Phytoestrogens and their health effect. Open Access Maced J Med Sci 2019; 7: 495–499.

[27] Qashqai H, Amanlou H, Amirabadi Farahani T, Farsuni NE, Khosravi Bakhtiary M. Effects of supplemental manganese on ovarian cysts incidence and reproductive performance in early lactation Holstein cows. Anim Feed Sci Technol 2020; 269: 114660.

[28] Canivenc-Lavier MC, Bennetau-Pelissero C. Phytoestrogens and health effects. Nutrients 2023; 15: 317.

[29] Al-Amoudi WM. Protective effects of fennel oil extract against sodium valproate-induced hepatorenal damage in albino rats. Saudi J Biol Sci 2017; 24: 915–924.

[30] Ibrahim MD, Alblesh MA, Al-Sugmiany RZ. Detection of active compounds in the water extract of Foeniculum Vulgare L. and its effects on serum estrogen and prolactin levels in female Albino rats. Iraqi J Sci 2021; 62: 3366–3371.

[31] Khazaei F, Naseri L, Akbaribazm M, Khazaei M. Foeniculum vulgare extract enhances estrogen levels, total antioxidant capacity, and protect ovarian histology in rats exposed to Bisphenol A. Endocrinol Res Pract 2023; 27: 227–232.

[32] Parandin R, Yousofvand N. [In utero and lactational effects of Aqueous Foeniculum Vulgare (Fennel) seed extract on puberty timing, estrus cycle and sexual behavior in mice]. J Arak Uni Med Sci 2018; 20: 1–12. (in Persian)

[33] Luan Y-Y, Zhang L, Peng Y-Q, Li Y-Y, Liu R-X, Yin Ch-H. Immune regulation in polycystic ovary syndrome. Clin Chim Acta 2022; 531: 265–272.

[34] Fozalaee SS, Farokhi F, Khaneshi F. [The effect of metformin and aqueous extract Foeniculum vulgare (fennel) on endometrial histomorphometry and the level of steroid hormones in rats with polycystic ovary syndrome]. Qom Univ Med Sci J 2015; 8 (Suppl.): 12–19. (in Persian)

[35] Abbas A, Ikram R, Hasan F, Sarfaraz S, Bukhari QUA. Fennel fortified diet: New perspective with regard to fertility and sex hormones. Pak J Pharm Sci 2020; 33: 2595–2600.

[36] Brozic P, Smuc T, Gobec S, Rizner TL. Phytoestrogens as inhibitors of the human progesterone metabolizing enzyme AKR1C1. Mol Cell Endocrinol 2006; 259: 30–42.

[37] Buck E, McNally L, Jenkins SM. Menstrual suppression. In: StatPearls. StatPearls publishing; 2023.

[38] Проданчук МГ, Татарчук ТФ, Гуньков СВ, Жмінько ПГ, Регеда СІ. [Impact of an increased exposure with manganese and nickel on pituitary hormones in women with ovarian polycystosis]. Reprod Endocrinol 2020; 53: 19–22. (in Russian)

[39] Fathi FH. Biomarkers of oxidative stress in polycystic ovary disorder. Ann Coll Med Mosul 2020; 41: 112–116.

[40] Hassanpour A, Yousefian S, Askaripour M, Sharififar F, Ezzatabadipour M. Ovarian protection in cyclophosphamide-treated mice by fennel. Toxicol Rep 2017; 4: 160–164.