DSS-induced colitis in WT, ERβ-KO, and ERα-KO male and female mice. Ten- to 12-week-old male (M) and female (F) WT, ERβ-KO, and ERα-KO mice were fed 2.5% DSS-supplemented drinking water for 5 days and killed on day 6. (A) Body weights were recorded at days 0, 5, and 6 and are expressed as the percentage of initial (day 0) weight. (B) The disease activity index (DAI) was calculated for each mouse at day 6 (encompassing body weight loss, stool consistency, and hemoccult scores). Analysis of variance (ANOVA) F = 36.3; P < .0001; α = .05 with 2 df. (C) Colon length was measured on day 6 (ANOVA F = 12.4; P < .0001, α = .05 with 2 df). (D) H&E-stained colon tissues collected from mice on day 6 were assessed for total inflammatory scores (TIS, encompassing ulceration; re-epithelization; active and chronic inflammation; and transmural inflammation; ANOVA F = 57.06 for interaction effects; P < .0001; α = .05 with 2 df). Data are represented as the means ± SEM of 7–17 individual mice/group; dots represent individual values. *P ≤ .05, **P ≤ .01, and ***P ≤ .001. (E) Endoscopic evaluations were performed of the descending colon on day 6, immediately before death. Arrows represent loss of transparency (red), bleeding (blue), and focal edematous lesions (green). (F) Distal colon tissues were harvested for H&E staining. Scale bar: 10 μm; original magnification, 10× + 1.25 numerical aperture (NA).