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