Beneficial effects of minocycline on the ovary of polycystic ovary syndrome mouse model: Molecular docking analysis and evaluation of TNF-α, TNFR2, TLR-4 gene expression

Autor: Mahdie Kian, Sorayya Ghasemi, Azadeh Khajouei, Tooba Abdizadeh, Elham Hosseini
Rok vydání: 2021
Předmět:
Ovulation
0301 basic medicine
medicine.medical_specialty
endocrine system diseases
media_common.quotation_subject
Immunology
Minocycline
Ovary
Pathogenesis
Mice
03 medical and health sciences
0302 clinical medicine
Internal medicine
Animals
Humans
Receptors
Tumor Necrosis Factor
Type II
Immunology and Allergy
Medicine
Testosterone
media_common
030219 obstetrics & reproductive medicine
Estradiol
Tumor Necrosis Factor-alpha
business.industry
Letrozole
Obstetrics and Gynecology
Polycystic ovary
female genital diseases and pregnancy complications
Molecular Docking Simulation
Toll-Like Receptor 4
Disease Models
Animal
030104 developmental biology
medicine.anatomical_structure
Endocrinology
Reproductive Medicine
Female
business
Corpus luteum
Polycystic Ovary Syndrome
Signal Transduction
medicine.drug
Zdroj: Journal of Reproductive Immunology. 144:103289
ISSN: 0165-0378
DOI: 10.1016/j.jri.2021.103289
Popis: Polycystic ovary syndrome (PCOS) is the most common cause of ovulatory infertility. Inflammation may be involved in the pathogenesis and development of PCOS. We investigated the anti-inflammatory effect of minocycline on TNF-α, TNFR2, and TLR4 expression levels and the key features of PCOS in a mouse model. Molecular docking was performed by Molecular Operating Environment software. PCOS was induced by estradiol valerate injection (EV) (2 mg/kg/day) in 40 mice. After 28 days, the mice were divided into five groups, including control, PCOS, minocycline control, minocycline PCOS model (50 mg/kg), and letrozole PCOS (0.5 mg/kg). The Levels of FSH, LH, E2, and testosterone were determined by ELISA. H&E staining was used for histological analysis in the ovarian tissues. Docking scores were -10.35, -10.57, and -12.45 kcal/mol for TNFα, TLR-4, and TNFR2, respectively. The expression levels of TNF-α, TNFR2, and TLR4 were detected by Real-Time PCR. PCOS models exhibited acyclicity, a significant increase in E2 levels (P < 0.01), and no difference in FSH, LH, and testosterone. The expression levels of TNF-α, TNFR2, and TLR-4 significantly increased in PCOS (2.70, 7.90, and 14.83-fold, respectively). EV treatment significantly increased graafian follicles (P < 0.001) and decreased corpus luteum (CL) (P < 0.01). Minocycline treatment in PCOS led to a significant decrease in E2 (P < 0.01) and graafian follicles (P < 0.001) and a significant increase in the CL numbers (P < 0.05). Our findings showed the positive effects of minocycline on estradiol level, CL and graafian follicles counts, suggesting that minocycline might inhibit these proteins and improve ovulation in our mouse model of PCOS.
Databáze: OpenAIRE
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