Interleukin-22 improves ovulation disorder via STAT3 signalling in polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disease which leads to serious impairment of reproductive health in women of child-bearing age. Anovulation or oligo-ovulation is a common clinical manifestation of PCOS patients. The disturbance of ovarian immune microenvironment contributes to the disorders of follicle development and ovulation, and the mechanism remains unclear. Here we demonstrated the protective effect of immune factor interleukin-22 (IL-22) on PCOS follicle development and ovulation. Follicular IL-22 levels were significantly lower in PCOS patients than in the control group and were positively correlated with the oocyte fertilization rate and the high-quality embryo rate. Additionally, IL-22 evidently improved follicle development in vitro and promoted ovulation-related gene expression, which was disrupted by the depletion of interleukin-22 receptor 1 (IL-22R1) or inhibition of STAT3 in granulosa cells, indicating that IL-22 acted through IL-22R1 and STAT3 signalling pathway to promote follicle development and ovulation in PCOS. In summary, this study elucidated the vital role of ovarian immune microenvironment in follicle development and ovulation, the application of IL-22 may provide new insights into the treatment of PCOS patients. Granulosa cells from Il22r+/+ or Il22r-/- mice were collected for RNA-sequencing, and there was three samples in Il22r+/+ and Il22r-/- group多囊卵巢综合征（Polycystic ovary syndrome, PCOS）是一种常见的生殖内分泌疾病，可对育龄女性的生殖健康造成严重损害。无排卵或稀发排卵是PCOS患者的常见临床表现。卵巢免疫微环境紊乱可引发卵泡发育与排卵异常，但其具体机制尚未明确。本研究证实了免疫因子白细胞介素-22（interleukin-22, IL-22）对PCOS患者卵泡发育及排卵的保护作用。PCOS患者的卵泡液IL-22水平显著低于对照组，且与卵母细胞受精率、优质胚胎率呈正相关。此外，IL-22可显著改善体外卵泡发育，并促进排卵相关基因的表达；而在颗粒细胞中敲除白细胞介素-22受体1（interleukin-22 receptor 1, IL-22R1）或抑制STAT3信号通路，可阻断上述效应，表明IL-22通过IL-22R1及STAT3信号通路促进PCOS的卵泡发育与排卵。综上，本研究阐明了卵巢免疫微环境在卵泡发育及排卵过程中的关键作用，IL-22的应用可为PCOS患者的治疗提供新的研究思路。本研究收集了Il22r+/+与Il22r-/-小鼠的颗粒细胞进行RNA测序，两组各包含3个样本。