An Experimental Study on The Oxidative Status and Inflammatory Levels of A Rat Model of Polycystic Ovary Syndrome Induced by Letrozole and A New High-Fat Diet

Document Type : Original Article

Authors

1 Department of Biology, Damghan Branch, Islamic Azad University, Damghan, Iran

2 School of Biology, Damghan University, Damghan, Iran

3 Department of Chemistry, Damghan Branch, Islamic Azad University, Damghan, Iran

Abstract

Background: Although there are numerous animal models of polycystic ovary syndrome (PCOS), they often fail to
accurately replicate the reproductive and metabolic phenotypes associated with PCOS. The objective of this study is
to assess oxidative status and inflammatory levels in a rat model of PCOS subjected to a new high-fat diet (HFD) in
combination with letrozole.
Materials and Methods: In this experimental study, mature, six-week-old female Sprague-Dawley rats (n=20) were
divided into four groups: control (standard diet); letrozole (letrozole plus a standard diet); HFD; and letrozole+HFD.
After 16 weeks, the rats underwent vaginal smear analysis, measurement of hormonal and lipid profiles, and an
oral glucose tolerance test (OGTT). Ovarian tissue morphology, oxidative parameters, and inflammatory status were
evaluated.
Results: The experimental groups exhibited anoestrus profiles in the vaginal smears and abnormal ovarian morphology,
which was not observed in the control group. Steroid hormone levels were significantly higher in the
letrozole+HFD group compared to the other groups (P=0.00). The experimental groups also showed abnormal glucose
levels and lipid metabolism. The relative expression levels of inflammatory genes were significantly elevated in
the experimental groups compared to the control group (P=0.00), and the letrozole+HFD group exhibited the highest
expression level (P=0.00). The HFD, letrozole, and letrozole+HFD groups demonstrated significantly increased levels
of malondialdehyde (MDA) and reactive oxygen species (ROS), while the levels of enzymatic antioxidants were
significantly reduced compared to the control group (P=0.00).
Conclusion: The combination of a new HFD and letrozole treatment induces inflammation and oxidative stress (OS)
in a rat model of PCOS. This model accurately exhibits abnormal metabolic phenotypes and disruptions in hormonal
profiles associated with PCOS.

Keywords

Main Subjects

References

  1. Mancini A, Bruno C, Vergani E, d'Abate C, Giacchi E, Silvestrini A. Oxidative stress and low-grade inflammation in polycystic ovary syndrome: controversies and new insights. Int J Mol Sci. 2021; 22(4): 1667.
  2. Hernández-Jiménez JL, Barrera D, Espinoza-Simón E, González J, Ortíz-Hernández R, Escobar L, et al. Polycystic ovarian syndrome: signs and feedback effects of hyperandrogenism and insulin resistance. Gynecol Endocrinol. 2022; 38(1): 2-9.
  3. Rizk MG, Thackray VG. Intersection of polycystic ovary syndrome and the gut microbiome. J Endocr Soc. 2020; 5(2): bvaa177.
  4. Chaudhary H, Patel J, Jain NK, Joshi R. The role of polymorphism in various potential genes on polycystic ovary syndrome susceptibility and pathogenesis. J Ovarian Res. 2021; 14(1): 125.
  5. Carvalho LML, Dos Reis FM, Candido AL, Nunes FFC, Ferreira CN, Gomes KB. Polycystic ovary syndrome as a systemic disease with multiple molecular pathways: a narrative review. Endocr Regul. 2018; 52(4): 208-221.
  6. Nehir Aytan A, Bastu E, Demiral I, Bulut H, Dogan M, Buyru F. Relationship between hyperandrogenism, obesity, inflammation and polycystic ovary syndrome. Gynecol Endocrinol. 2016; 32(9): 709-713.
  7. Osuka S, Nakanishi N, Murase T, Nakamura T, Goto M, Iwase A, et al. Animal models of polycystic ovary syndrome: A review of hormone-induced rodent models focused on hypothalamus-pituitary-ovary axis and neuropeptides. Reprod Med Biol. 2018; 18(2): 151-160.
  8. Wang MX, Yin Q, Xu X. A rat model of polycystic ovary syndrome with insulin resistance induced by letrozole combined with high fat diet. Med Sci Monit. 2020; 26: e922136.
  9. Zhang H, Yi M, Zhang Y, Jin H, Zhang W, Yang J, et al. High-fat diets exaggerate endocrine and metabolic phenotypes in a rat model of DHEA-induced PCOS. Reproduction. 2016; 151(4): 431-441.
  10. Reddy P, Begum N, Mutha S, Bakshi V. Beneficial effect of curcumin in letrozole induced polycystic ovary syndrome. Asian Pac J Reprod. 2016; 5(2): 116-122.
  11. Ryu Y, Kim SW, Kim YY, Ku SY. Animal models for human polycystic ovary syndrome (PCOS) focused on the use of indirect hormonal perturbations: a review of the literature. Int J Mol Sci. 2019; 20(11): 2720.
  12. Wu S, Divall S, Nwaopara A, Radovick S, Wondisford F, Ko C, et al. Obesity-induced infertility and hyperandrogenism are corrected by deletion of the insulin receptor in the ovarian theca cell. Diabetes. 2014; 63(4): 1270-1282.
  13. Bagheripour N, Zavareh S, Ghorbanian MT, Paylakhi SH, Mohebbi SR. Changes in the expression of OCT4 in mouse ovary during estrous cycle. Vet Res Forum. 2017; 8(1): 43-48.
  14. Myers M, Britt KL, Wreford NG, Ebling FJ, Kerr JB. Methods for quantifying follicular numbers within the mouse ovary. Reproduction. 2004; 127(5): 569-580.
  15. Nasiri M, Saadat M, Karimi MH, Azarpira N, Saadat I. Evaluating mRNA Expression Levels of the TLR4/IRF5 Signaling Axis During Hepatic Ischemia-Reperfusion Injuries. Exp Clin Transplant. 2019; 17(5): 648-652.
  16. Hosseinzadeh E, Zavareh S, Lashkarbolouki T. Antioxidant properties of coenzyme Q10-pretreated mouse pre-antral follicles derived from vitrified ovaries. J Obstet Gynaecol Res. 2017; 43(1): 140-148.
  17. Talebi A, Zavareh S, Kashani MH, Lashgarbluki T, Karimi I. The effect of alpha lipoic acid on the developmental competence of mouse isolated preantral follicles. J Assist Reprod Genet. 2012; 29(2): 175-183.
  18. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951; 193(1): 265-275.
  19. Xu J, Dun J, Yang J, Zhang J, Lin Q, Huang M, et al. Letrozole rat model mimics human polycystic ovarian syndrome and changes in insulin signal pathways. Med Sci Monit. 2020; 26: e923073.
  20. Ressler IB, Grayson BE, Ulrich-Lai YM, Seeley RJ. Diet-induced obesity exacerbates metabolic and behavioral effects of polycystic
  21. 2015; 308(12): E1076-E1084.
  22. Patel R, Shah G. High-fat diet exposure from pre-pubertal age induces polycystic ovary syndrome (PCOS) in rats. Reproduction. 2018; 155(2): 141-151.
  23. Lai H, Jia X, Yu Q, Zhang C, Qiao J, Guan Y, et al. High-fat diet induces significant metabolic disorders in a mouse model of polycystic ovary syndrome. Biol Reprod. 2014; 91(5): 127.
  24. Festa A, D'Agostino R Jr, Howard G, Mykkänen L, Tracy RP, Haffner SM. Chronic subclinical inflammation as part of the insulin resistance syndrome: the Insulin Resistance Atherosclerosis Study (IRAS). Circulation. 2000; 102(1): 42-47.
  25. González F, Rote NS, Minium J, Kirwan JP. Increased activation of nuclear factor kappaB triggers inflammation and insulin resistance in polycystic ovary syndrome. J Clin Endocrinol Metab. 2006; 91(4): 1508-1512.

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