Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China.
Key Laboratory of Assisted Reproduction (Peking University), Ministry of Education, Beijing, China.
J Endocrinol. 2020 May;245(2):281-289. doi: 10.1530/JOE-19-0589.
Polycystic ovary syndrome (PCOS) is a complex syndrome involving both endocrine and metabolic disorders. Gut microbiota and the intestinal immune factor IL-22 play an important role in the pathogenesis of PCOS. However, the therapeutic role of IL-22 in high androgen-induced PCOS mice is not clear. We aimed to determine the therapeutic effects of IL-22 on the DHEA-induced PCOS mouse model and to explore the possible mechanism of IL-22 in regulating hyperandrogenism-associated PCOS. Insulin resistance levels and ovarian functions were investigated in DHEA-induced PCOS mice with or without additional IL-22 treatment. We found that IL-22 could reverse insulin resistance, disturbed estrous cycle, abnormal ovary morphology, and decreased embryo number in DHEA mice. Mechanistically, IL-22 upregulated the browning of white adipose tissue in DHEA mice. This study demonstrated that IL-22-associated browning of white adipose tissue regulated insulin sensitivity and ovarian functions in PCOS, suggesting that IL-22 may be of value for the treatment of PCOS with a hyperandrogenism phenotype.
多囊卵巢综合征(PCOS)是一种涉及内分泌和代谢紊乱的复杂综合征。肠道微生物群和肠道免疫因子 IL-22 在 PCOS 的发病机制中发挥重要作用。然而,IL-22 在高雄激素诱导的 PCOS 小鼠中的治疗作用尚不清楚。我们旨在确定 IL-22 对 DHEA 诱导的 PCOS 小鼠模型的治疗作用,并探讨 IL-22 调节与高雄激素相关的 PCOS 的可能机制。用或不用额外的 IL-22 治疗,研究了 DHEA 诱导的 PCOS 小鼠的胰岛素抵抗水平和卵巢功能。我们发现,IL-22 可以逆转 DHEA 小鼠的胰岛素抵抗、发情周期紊乱、卵巢形态异常和胚胎数量减少。在机制上,IL-22 上调了 DHEA 小鼠白色脂肪组织的棕色化。这项研究表明,IL-22 相关的白色脂肪组织棕色化调节了 PCOS 中的胰岛素敏感性和卵巢功能,提示 IL-22 可能对治疗具有高雄激素表型的 PCOS 具有价值。