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

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.