Department of Obstetrics and Gynecology, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei 111, Taiwan.
Department of Obstetrics and Gynecology, School of Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan.
Int J Mol Sci. 2021 Dec 23;23(1):134. doi: 10.3390/ijms23010134.
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.
多囊卵巢综合征（PCOS）影响着 5-10%的育龄妇女，其与生殖和代谢紊乱有关，如慢性无排卵、不孕、胰岛素抵抗和 2 型糖尿病。然而，PCOS 的发病机制仍不清楚。因此，本研究采用了来曲唑暴露的小鼠模型，通过对小鼠进行为期 20 周的口服来曲唑给药，以研究来曲唑对来曲唑诱导的 PCOS 小鼠生殖和代谢后果严重程度以及半胱氨酸-半胱氨酸基序趋化因子受体 5（CCR5）表达的影响。来曲唑处理的小鼠表现出发情周期紊乱，并停留在动情前期。来曲唑处理还增加了血浆睾丸酮水平，降低了雌二醇水平，并导致多滤泡形成。此外，对卵巢旁白色脂肪组织（pgWAT）的组织学分析显示，来曲唑处理组和对照组之间脂肪细胞的大小和数量没有显著差异。此外，在口服葡萄糖和胰岛素耐量试验中，来曲唑处理的小鼠表现出葡萄糖不耐受和胰岛素抵抗。此外，pgWAT 中 CCR5 和半胱氨酸-半胱氨酸基序配体 5（CCL5）的表达在来曲唑处理组小鼠中明显高于对照组。CCR5 和 CCL5 与稳态模型评估的胰岛素抵抗（HOMA-IR）也显著相关。最后，PCOS 中胰岛素抵抗的机制可能是由于丝氨酸磷酸化增加和 Akt 磷酸化减少所致。
