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.