Molecular docking and mouse modeling suggest CMKLR1 and INSR as targets for improving PCOS phenotypes by minocycline

Authors

  • Mahdie Kian Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran https://orcid.org/0000-0001-9228-0414
  • Elham Hosseini Department of Obstetrics and Gynecology, IVF Clinic, Mousavi Hospital, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran https://orcid.org/0000-0002-3494-6262
  • Tooba Abdizadeh Clinical Biochemistry Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran https://orcid.org/0000-0003-2715-562X
  • Taimour Langaee Center for Pharmacogenomics and Precision Medicine, College of Pharmacy, University of Florida, Gainesville, FL, USA https://orcid.org/0000-0001-5040-6365
  • Azadeh Khajouei Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran https://orcid.org/0000-0002-1849-4964
  • Sorayya Ghasemi Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran; Tel: 09131856090, 03833331471; E-mails: s.ghasemi@skums.ac.ir; sorayya.ghasemi@gmail.com https://orcid.org/0000-0001-9986-4930

DOI:

https://doi.org/10.17179/excli2021-4534

Keywords:

PCOS, INSR, CMKLR1, minocycline, inflammation

Abstract

Polycystic ovary syndrome (PCOS) is the most common cause of women’s infertility. Some inflammatory pathways play a pivotal role in the pathogenesis of PCOS. This study aimed to investigate the possible beneficial effects of minocycline on chemokine-like receptor 1 (CMKLR1) and Insulin Receptor (INSR) in a PCOS model. A molecular docking study was implemented using Molecular Operating Environment (MOE) software. The PCOS was induced in NMRI mice (mean body weight 14.47±0.23) by 28 days estradiol valerate injection (2 mg/kg/day). The mice were then divided into six groups (n=8 per group, mean body weight 17.77± 0.26): control (received normal saline), PCOS model, control for minocycline, minocycline treated PCOS (50 mg/kg), letrozole treated PCOS (0.5 mg/kg), and metformin-treated PCOS (300 mg/kg). Serum FSH, LH, estradiol (E2), and testosterone were detected by ELISA. The ovarian tissues were stained by hematoxylin and eosin. The CMKLR1 and INSR expression levels were determined by Real-time-PCR. The molecular docking studies showed scores of -10.92 and -9.30 kcal/mol, respectively, for minocycline with CMKLR1 and INSR. Estradiol valerate treatment led to a significant increase in E2, graffian follicle, and decrease in corpus luteum (CL) numbers (P<0.05), while minocycline treatment improved these PCOS features. The minocycline treatment significantly decreased the CMKLR1 expression and increased the INSR expression (P<0.05) while the CMKLR1 expression was increased in PCOS model. Minocycline may improve ovulation in PCOS model by returning E2 to a normal level and increasing CL number (ovulation signs). These beneficial outcomes may be related to the changes in CMKLR1 and INSR gene expression involved in glucose metabolism and inflammation.

Author Biographies

Tooba Abdizadeh, Clinical Biochemistry Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran

 E-mail: t.abdizadeh@gmail.com; abdizadeh.t@skums.ac.ir, ORCID: https://orcid.org/0000-0003-2715-562X

Taimour Langaee, Center for Pharmacogenomics and Precision Medicine, College of Pharmacy, University of Florida, Gainesville, FL, USA

E-mail: Langaee@cop.ufl.edu

ORCID: https://orcid.org/0000-0001-5040-6365

Sorayya Ghasemi, Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran; Tel: 09131856090, 03833331471; E-mails: s.ghasemi@skums.ac.ir; sorayya.ghasemi@gmail.com

E-mail: s.ghasemi@skums.ac.ir, sorayya.ghasemi@gmail.com; ORCID: https://orcid.org/ 0000-0001-9986-4930

Downloads

Additional Files

Published

2022-02-16

How to Cite

Kian, M., Hosseini, E., Abdizadeh, T., Langaee, T., Khajouei, A., & Ghasemi, S. (2022). Molecular docking and mouse modeling suggest CMKLR1 and INSR as targets for improving PCOS phenotypes by minocycline. EXCLI Journal, 21, 400–414. https://doi.org/10.17179/excli2021-4534

Issue

Vol. 21 (2022)

Section

Original articles

Categories

License

Copyright (c) 2022 Mahdie Kian, Elham Hosseini, Tooba Abdizadeh, Taimour Langaee, Azadeh Khajouei, Sorayya Ghasemi

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Authors who publish in this journal agree to the following terms:

  • The authors keep the copyright and grant the journal the right of first publication under the terms of the Creative Commons Attribution license, CC BY 4.0. This licencse permits unrestricted use, distribution and reproduction in any medium, provided that the original work is properly cited.
  • The use of general descriptive names, trade names, trademarks, and so forth in this publication, even if not specifically identified, does not imply that these names are not protected by the relevant laws and regulations.
  • Because the advice and information in this journal are believed to be true and accurate at the time of publication, neither the authors, the editors, nor the publisher accept any legal responsibility for any errors or omissions presented in the publication. The publisher makes no guarantee, express or implied, with respect to the material contained herein.
  • The authors can enter into additional contracts for the non-exclusive distribution of the journal's published version by citing the initial publication in this journal (e.g. publishing in an institutional repository or in a book).