The Effects of AdipoRon on Cytochrome P450-related Gene Expression, Acute Steroidogenic Regulatory Protein, and Structure of Ovary in Polycystic Ovary Syndrome Model

Overview

Journal J Assist Reprod Genet

Publisher Springer

Specialties Genetics
Reproductive Medicine

Date 2023 Sep 5

PMID 37668858

Authors

Pegah Hazrati

Mahdi Ramezani

Davoud Ahmadimoghaddam

Sara Soleimani Asl

Tayebe Artimani

Affiliations

Soon will be listed here.

Abstract

Purpose: One of the most common causes of infertility in adult women is polycystic ovary syndrome (PCOS) which has been identified with symptoms such as chronic hyperandrogenism, anovulation, and polycystic ovaries. Adiponectin modulates steroidogenesis and the expression of ovulation-related genes. Herein, we assessed the effect of AdipoRon (adiponectin agonist) in the PCOS model mice.

Methods: The PCOS model was induced with letrozole in the adult female mice and the animals received intraperitoneal injection of AdipoRon (5 mg/kg) for 10 days. Expression of CYP11A, CYP17A, and CYP19A genes, StAR protein, and histomorphology of the ovary were evaluated using real-time RT-PCR, western blotting, and histochemistry methods, respectively.

Results: Although administration of letrozole caused an increase in the expression of CYP11A, CYP17A, and StAR and a decrease in the CYP19A1 expression, injection of AdipoRon reversed these changes. Moreover, AdipoRon treatment resulted in an improvement of folliculogenesis and a reduction of cysts compared to the letrozole-treated mice.

Conclusion: It is likely that AdipoRon has protective effects on the PCOS through modulation of cytochrome P450-related genes and steroidogenesis but needs further study to be sure.

Citing Articles

Chiglitazar ameliorates dehydroepiandrosterone-induced polycystic ovary syndrome in rats.

Zhao F, Cui W, Fang C, Luo Y, Zhang C J Ovarian Res. 2024; 17(1):229.

PMID: 39563391 PMC: 11575166. DOI: 10.1186/s13048-024-01554-6.

Exploring the logic and conducting a comprehensive evaluation of AdipoRon-based adiponectin replacement therapy against hormone-related cancers-a systematic review.

Fornari Laurindo L, Sosin A, Lamas C, de Alvares Goulart R, Dos Santos Haber J, Rucco Penteado Detregiachi C Naunyn Schmiedebergs Arch Pharmacol. 2023; 397(4):2067-2082.

PMID: 37864589 DOI: 10.1007/s00210-023-02792-z.

References

Franks S . Polycystic ovary syndrome. N Engl J Med. 1995; 333(13):853-61. DOI: 10.1056/NEJM199509283331307. View

Himelein M, Thatcher S . Polycystic ovary syndrome and mental health: A review. Obstet Gynecol Surv. 2006; 61(11):723-32. DOI: 10.1097/01.ogx.0000243772.33357.84. View

Goodarzi M, Dumesic D, Chazenbalk G, Azziz R . Polycystic ovary syndrome: etiology, pathogenesis and diagnosis. Nat Rev Endocrinol. 2011; 7(4):219-31. DOI: 10.1038/nrendo.2010.217. View

Diamanti-Kandarakis E, Dunaif A . Insulin resistance and the polycystic ovary syndrome revisited: an update on mechanisms and implications. Endocr Rev. 2012; 33(6):981-1030. PMC: 5393155. DOI: 10.1210/er.2011-1034. View

Zeng X, Xie Y, Liu Y, Long S, Mo Z . Polycystic ovarian syndrome: Correlation between hyperandrogenism, insulin resistance and obesity. Clin Chim Acta. 2019; 502:214-221. DOI: 10.1016/j.cca.2019.11.003. View

Rosenfield R, Ehrmann D . The Pathogenesis of Polycystic Ovary Syndrome (PCOS): The Hypothesis of PCOS as Functional Ovarian Hyperandrogenism Revisited. Endocr Rev. 2016; 37(5):467-520. PMC: 5045492. DOI: 10.1210/er.2015-1104. View

Wawrzkiewicz-Jalowiecka A, Kowalczyk K, Trybek P, Jarosz T, Radosz P, Setlak M . In Search of New Therapeutics-Molecular Aspects of the PCOS Pathophysiology: Genetics, Hormones, Metabolism and Beyond. Int J Mol Sci. 2020; 21(19). PMC: 7582580. DOI: 10.3390/ijms21197054. View

Aghaie F, Khazali H, Hedayati M, Akbarnejad A . The Effects of Exercise on Expression of CYP19 and StAR mRNA in Steroid-Induced Polycystic Ovaries of Female Rats. Int J Fertil Steril. 2017; 11(4):298-303. PMC: 5641462. DOI: 10.22074/ijfs.2018.5035. View

Okada-Iwabu M, Yamauchi T, Iwabu M, Honma T, Hamagami K, Matsuda K . A small-molecule AdipoR agonist for type 2 diabetes and short life in obesity. Nature. 2013; 503(7477):493-9. DOI: 10.1038/nature12656. View

10.

Galluzzo A, Calogero Amato M, Giordano C . Insulin resistance and polycystic ovary syndrome. Nutr Metab Cardiovasc Dis. 2008; 18(7):511-8. DOI: 10.1016/j.numecd.2008.05.004. View

11.

Maliqueo M, Sun M, Johansson J, Benrick A, Labrie F, Svensson H . Continuous administration of a P450 aromatase inhibitor induces polycystic ovary syndrome with a metabolic and endocrine phenotype in female rats at adult age. Endocrinology. 2012; 154(1):434-45. DOI: 10.1210/en.2012-1693. View

12.

Kafali H, Iriadam M, Ozardali I, Demir N . Letrozole-induced polycystic ovaries in the rat: a new model for cystic ovarian disease. Arch Med Res. 2004; 35(2):103-8. DOI: 10.1016/j.arcmed.2003.10.005. View

13.

Monsef F, Artimani T, Ramazani M, Alizadeh Z, Solgi G, Yavangi M . Effects of adipose- derived stromal vascular fraction on asherman syndrome model. Acta Histochem. 2020; 122(5):151556. DOI: 10.1016/j.acthis.2020.151556. View

14.

Goharitaban S, Amiri I, Asl S, Saidijam M, Yavangi M, Khanlarzadeh E . Abnormal expressions of ADAMTS-1, ADAMTS-9 and progesterone receptors are associated with lower oocyte maturation in women with polycystic ovary syndrome. Arch Gynecol Obstet. 2018; 299(1):277-286. DOI: 10.1007/s00404-018-4967-2. View

15.

Brennan K, Huang A, Azziz R . Dehydroepiandrosterone sulfate and insulin resistance in patients with polycystic ovary syndrome. Fertil Steril. 2008; 91(5):1848-52. PMC: 2691796. DOI: 10.1016/j.fertnstert.2008.02.101. View

16.

Goodarzi M, Carmina E, Azziz R . DHEA, DHEAS and PCOS. J Steroid Biochem Mol Biol. 2014; 145:213-25. DOI: 10.1016/j.jsbmb.2014.06.003. View

17.

Guo I, Shih M, Lan H, Hsu N, Hu M, Chung B . Transcriptional regulation of human CYP11A1 in gonads and adrenals. J Biomed Sci. 2007; 14(4):509-15. DOI: 10.1007/s11373-007-9177-z. View

18.

Franks S, Gharani N, Waterworth D, Batty S, White D, Williamson R . The genetic basis of polycystic ovary syndrome. Hum Reprod. 1998; 12(12):2641-8. DOI: 10.1093/humrep/12.12.2641. View

19.

Qin K, Rosenfield R . Role of cytochrome P450c17 in polycystic ovary syndrome. Mol Cell Endocrinol. 1999; 145(1-2):111-21. DOI: 10.1016/s0303-7207(98)00177-4. View

20.

Shen W, Li T, Hu Y, Liu H, Song M . Common polymorphisms in the CYP1A1 and CYP11A1 genes and polycystic ovary syndrome risk: a meta-analysis and meta-regression. Arch Gynecol Obstet. 2013; 289(1):107-18. DOI: 10.1007/s00404-013-2939-0. View