Cysteine–Cysteine Motif Chemokine Receptor 5 Expression in Letrozole-Induced Polycystic Ovary Syndrome Mice

Abstract

Polycystic ovary syndrome (PCOS), which affects 5–10% of women of reproductive age, is associated with reproductive and metabolic disorders, such as chronic anovulation, infertility, insulin resistance, and type 2 diabetes. However, the mechanism of PCOS is still unknown. Therefore, this study used a letrozole-exposed mouse model in which mice were orally fed letrozole for 20 weeks to investigate the effects of letrozole on the severity of reproductive and metabolic consequences and the expression of cysteine–cysteine motif chemokine receptor 5 (CCR5) in letrozole-induced PCOS mice. The letrozole-treated mice showed a disrupted estrous cycle and were arrested in the diestrus phase. Letrozole treatment also increased plasma testosterone levels, decreased estradiol levels, and caused multicystic follicle formation. Furthermore, histological analysis of the perigonadal white adipose tissue (pgWAT) showed no significant difference in the size and number of adipocytes between the letrozole-treated mice and the control group. Further, the letrozole-treated mice demonstrated glucose intolerance and insulin resistance during oral glucose and insulin tolerance testing. Additionally, the expression of CCR5 and cysteine-cysteine motif ligand 5 (CCL5) were significantly higher in the pgWAT of the letrozole-treated mice compared with the control group. CCR5 and CCL5 were also significantly correlated with the homeostasis model assessment of insulin resistance (HOMA-IR). Finally, the mechanisms of insulin resistance in PCOS may be caused by an increase in serine phosphorylation and a decrease in Akt phosphorylation.

Regulation of Insulin Resistance, Lipid Profile and Glucose Metabolism Associated with Polycystic Ovary Syndrome by Tinospora cordifolia

“…These are in line with the study in which supplementation with TC extracts has been shown to significantly reduce the risk of morphological abnormalities in the ovaries due to radiation exposure [52]. Hypertrophy, as well as the formation of black patches and granular alterations, were observed in previous research, and these may be seen with the naked eye after DHEA treatment [50]. Treatment with metformin reduced the black spots and granulation but not as well as in TC-treated groups.…”

“…The mechanism whereby the active components of TC increase muscle glucose absorption is supported by the Insulin Sensitivity Index QUICKI. Treatment with TC oil and HA extracts demonstrated a dose-dependent improvement in the activity of beta cells, reflected in the HOMA-Beta values [ 50 ]. These findings are consistent with earlier findings that TC reduced fructose-induced increases in blood sugar, insulin, and triglycerides.…”

Western‐style diet in the presence of elevated circulating testosterone induces adipocyte hypertrophy without proinflammatory responses in rhesus macaques

“…41,42 CCL5 levels in the blood and visceral WAT have been shown to be elevated in letrozole-induced PCOS in mice and in PCOS patients. 43,44 Our previous study showed that T+WSD treatment or the consumption of WSD alone for 3 years was associated with elevated CRP levels in female rhesus macaques, 10 suggesting that longer treatment is necessary for inducing a systemic proinflammatory response in NHPs.…”

Therapeutic Effect of Tinospora cordifolia (Willd) Extracts on Letrozole-Induced Polycystic Ovarian Syndrome and its Complications in Murine Model

“…These findings are consistent with earlier findings that TC reduced fructose-induced increased blood sugar, insulin and triglycerides. 49 Recently published study on berberine alkaloid which is also an important chemical constituent discovered in the TC plant stem has been shown to significantly enhance glucose tolerance. 50 Treatment with berberine significantly reduces fasting plasma glucose, improves insulin sensitivity and decreases LDL-C in type 2 diabetic rats, demonstrating its potent antihyperglycaemic and hypolipidemic effects.…”