Fig 1: IL-22 alleviates DHEA-induced PCOS by inhibition of ferroptosis via STAT3 activation.A, B Representative images of TUNEL-stained ovarian sections (scale bar: 50 μm). C, D Representative Western blot images of PTGS2 and GPX4 in ovarian tissues. Band quantification is normalized to the first lane. E KGN cells were pretreated with 1 μM ferrostatin-1 (Fer-1) with or without 0.1 μg/mL rMuIL-22 for 2 h, followed by DHEA (20 μM) treatment for 24 h. Cell viability was assessed using the CCK-8 assay (n = 5 biological replicates per group). F Representative H&E-stained ovarian tissue sections (scale bar: 200 μm). G Quantification of cystic follicles and corpora lutea (n = 5 mice per group). H Representative Western blot images of p-STAT3 and total STAT3 in ovarian tissues of rMuIL-22-treated mice. Band quantification is normalized to the first lane (p-STAT3/STAT3). I, J KGN cells were treated with 20 μM Stattic for 1 h, followed by rMuIL-22 (0.1 μg/mL) for 2 h, and then DHEA (20 μM) for 24 h. I Cell viability (n = 6 biological replicates per group). J Representative images of PTGS2 and GPX4. Band quantification is normalized to the first lane. K GTT and ITT assays (n = 5 mice per group). GTT: ##p = 0.0097 (15 min), ###p = 0.0006 (30 min), ##p = 0.0019 (60 min) and ##p = 0.0046 (90 min) for rMuIL-22 + Stattic + Neu5Ac + DHEA vs rMuIL-22 + Neu5Ac + DHEA. ITT: #p = 0.0412 (60 min) for rMuIL-22 + Stattic + Neu5Ac + DHEA vs rMuIL-22 + Neu5Ac + DHEA. L Representative H&E-stained images (scale bar: 200 μm). M Quantification of cystic follicles and corpora lutea (n = 5 mice per group). Data are presented as mean ± SD. One-way ANOVA followed by Tukey’s post hoc test (E, G, I, and M), and two-way repeated-measures ANOVA with Sidak’s multiple-comparisons correction (K) were performed. TUNEL-stained and Western blot images are representative of at least three biologically independent experiments with consistent results (A–D, H, and J).