Cysteine–cysteine motif chemokine receptor 5 expression in letrozole-induced polycystic ovary syndrome mice

Kok Min Seow, Pin Shiou Liu, Kuo Hu Chen, Chien Wei Chen, Luen Kui Chen, Chi Hong Ho, Jiann Loung Hwang, Peng Hui Wang, Chi Chang Juan*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number134
JournalInternational Journal Of Molecular Sciences
Volume23
Issue number1
DOIs
StatePublished - 1 Jan 2022

Keywords

  • CCL5
  • CCR5
  • Letrozole
  • Polycystic ovary syndrome

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