Improved hormonal and oxidative changes by Royal Jelly in the rat model of PCOS: An experimental study


Background: Polycystic ovarian syndrome (PCOS) is an endocrine and complex metabolic disorder, associated with anovulation, changes in sex hormone, biochemical factors, and ovarian tissue. Royal Jelly (RJ) has antioxidant and anti-inflammatory properties.

Objective: To examine the therapeutic effect of RJ on PCOS-related hormonal and biochemical changes in a rat model of PCOS.

Materials and Methods: In this experimental study, 42 female Wistar rats (weighing 180–200 gr, aged 10–12 wk) were divided into six groups (n = 7/each): control; PCOS; RJ 100 mg/kg; RJ 200 mg/kg; PCOS + RJ 100 mg/kg; and PCOS + RJ 200 mg/kg. After 21 days, the animals were weighed and dissected. The serums were used for nitric oxide (NO) and ferric-reducing antioxidant power (FRAP) assay and estradiol and progesterone measurements. The ovaries were assessed for histological changes.

Results: PCOS increased estradiol and NO levels, and decreased progesterone and FRAP levels. In PCOS + RJ groups, the progesterone (p = 0.01) and FRAP levels (p ≤ 0.001) increased and the estradiol and NO (p ≤ 0.001) levels decreased significantly. Moreover, the number of mature follicles (p = 0.01) and corpus luteum increased (p ≤ 0.001), and ovarian and uterus weight deceased significantly (p ≤ 0.001).

Conclusion: RJ improved estradiol, progesterone, FRAP, and NO levels, and ovarian structure in the rat model of PCOS.

Key words: Royal Jelly, Polycystic ovary syndrome, Ovary, Sex hormone.

[1] Pundir J, Charles D, Sabatini L, Hiam D, Jitpiriyaroj S, Teede H, et al. Overview of systematic reviews of non-pharmacological interventions in women with polycystic ovary syndrome. Hum Reprod Update 2019; 25: 243–256.

[2] Naseri L, Khazaei MR, Khazaei M. Synergic effect of bee pollen and metformin on proliferation and apoptosis of granulosa cells: Rat model of polycystic ovary syndrome. J Food Biochem 2021: e13635.

[3] Kohzadi M, Khazaei MR, Choobsaz F, Kazaei M. Relationship between serum levels of anti-mullerian hormone, adiponectin and oxidative stress markers in patients with polycystic ovary syndrome. Int J Fertil Steril 2020; 14: 27–33.

[4] Papalou O, Victor VM, Diamanti-Kandarakis E. Oxidative stress in polycystic ovary syndrome. Curr Pharm Des 2016; 22: 2709–2722.

[5] Borzoei A, Rafraf M, Niromanesh Sh, Farzadi L, Narimani F, Doostan F. Effects of cinnamon supplementation on antioxidant status and serum lipids in women with polycystic ovary syndrome. J Tradit Complement Med 2017; 8: 128–133.

[6] Hassani F, Karami M, Jalali Nadoushan MR, Eftekhari Yazdi P. Nitric oxide-induced polycystic ovaries in the Wistar rat. Int J Fertil Steril 2012; 6: 111–116.

[7] Basini G, Grasselli F. Nitric oxide in follicle development and oocyte competence. Reproduction 2015; 150: 1–9.

[8] Hu S, Yu Q, Wang Y, Wang M, Xia W, Zhu C. Letrozole versus clomiphene citrate in polycystic ovary syndrome: A meta-analysis of randomized controlled trials. Arch Gynecol Obstet 2018; 297: 1081–1088. [

9] Khazaei M, Ansarian A, Ghanbari E. New findings on biological actions and clinical applications of Royal Jelly: A review. J Diet Suppl 2018; 15: 757–775.

[10] Husein MQ, Haddad SG. A new approach to enhance reproductive performance in sheep using Royal Jelly in comparison with equine chorionic gonadotropin. Anim Reprod Sci 2006; 93: 24–33.

[11] Sosa-Pérez G, Pérez-Ruiz E, Pérez-Hernández P, Cortez-Romero C, Gallegos-Sánchez J. Intravenous administration of Royal Jelly in ovarian activity and ovulatory rate of Pelibuey sheep. Agroproductividad 2017; 10: 42–46.

[12] Ghanbari E, Khazaei MR, Khazaei M, Nejati V. Royal Jelly promotes ovarian follicles growth and increases steroid hormones in immature rats. Int J Fertil Steril 2018; 11: 263–269.

[13] Valiollahpoor Amiri M, Deldar H, Ansari Pirsaraei Z. Impact of supplementary Royal Jelly on in vitro maturation of sheep oocytes: Genes involved in apoptosis and embryonic development. Syst Biol Reprod Med 2016; 62: 31–38.

[14] Veshkini A, Mohammadi-Sangcheshmeh A, Ghanem N, Abazari-kia AH, Mottaghi E, Kamaledini R, et al. Oocyte maturation with Royal Jelly increases embryo development and reduces apoptosis in goats. Anim Reprod 2018; 15: 124–134.

[15] Khazaei M, Pazhouhi M, Khazaei S. Evaluation of hydro-alcoholic extract of Trifolium Pratens L. for its anti-cancer potential on U87MG Cell line. Cell J 2018; 20: 412–421.

[16] Khazaei M, Roshankhah S, Ghorbani R, Chobsaz F. Sildenafil effect on nitric oxide secretion by normal human endometrial epithelial cells cultured in vitro. Int J Fertil Steril 2011; 5: 142–147.

[17] Naseri L, Khazaei MR, Khazaei M. Potential therapeutic effect of bee pollen and metformin combination on testosterone and estradiol levels, apoptotic markers and total antioxidant capacity in a rat model of polycystic ovary syndrome. Int J Fertil Steril 2021; 15: 101–107.

[18] Khazaei F, Ghanbari E, Khazaei M. Protective effect of Royal Jelly against cyclophosphamide-induced thrombocytopenia and spleen and bone marrow damages in rats. Cell J 2020; 22: 302–309.

[19] Jelodar G, Masoomi S, Rahmanifar F. Hydroalcoholic extract of flaxseed improves polycystic ovary syndrome in a rat model. Iran J Basic Med Sci 2018; 21: 645–650.

[20] Desai V, Prasad NR, Manohar SM, Sachan A, Narasimha SRPVL, Bitla ARR. Oxidative stress in nonobese women with polycystic ovarian syndrome. J Clin Diagn Res 2014; 8: CC01–CC03.

[21] Moti M, Amini L, Mirhoseini Ardakani SS, Kamalzadeh S, Masoomikarimi M, Jafarisani M. Oxidative stress and anti-oxidant defense system in Iranian women with polycystic ovary syndrome. Iran J Reprod Med 2015; 13: 373–378.

[22] Rosenfield RL, Ehrmann DA. The pathogenesis of polycystic ovary syndrome (PCOS): The hypothesis of PCOS as functional ovarian hyperandrogenism revisited. Endocr Rev 2016; 37: 467–520.

[23] Nath P, Maitra S. Physiological relevance of nitric oxide in ovarian functions: An overview. Gen Comp Endocrinol 2019; 279: 35–44.

[24] Olson LM, Jones-Burton CM, Jablonka-Shariff A. Nitric oxide decreases estradiol synthesis of rat luteinized ovarian cells: Possible role for nitric oxide in functional luteal regression. Endocrinology 1996; 137: 3531–3539.

[25] Kocot J, Kiełczykowska M, Luchowska-Kocot D, Kurzepa J, Musik I. Antioxidant potential of propolis, bee pollen, and Royal Jelly: Possible medical application. Oxid Med Cell Longev 2018; 2018: 7074209. 1–29.

[26] Murri M, Insenser M, Escobar-Morreale HF. Metabolomics in polycystic ovary syndrome. Clin Chim Acta 2014; 429: 181–188.

[27] Zafari Zangeneh F, Minaee B, Amirzargar A, Ahangarpour A, Mousavizadeh K. Effects of chamomile extract on biochemical and clinical parameters in a rat model of polycystic ovary syndrome. J Reprod Infertil 2010; 11: 169–174.

[28] Reynolds LP, Grazul−Bilska AT, Redmer DA. Angiogenesis in the female reproductive organs: Pathological implications. Int J Exp Pathol 2002; 83: 151–164.