Fig. 2: Prenatal AE causes transgenerational hyperglycemia and glucose intolerance in F1‒F3 male offspring that are aggravated by advanced age and high-fat diet.

a Schematic illustration of the experimental design of the mouse models. b Fed blood glucose levels in F1‒F4 male offspring at the indicated ages. Ctrl-NCD-8w (F1: n = 8; F2: n = 14; F3: n = 7; F4: n = 9); AE-NCD-8w (F1: n = 13; F2: n = 12; F3: n = 8; F4: n = 13); Ctrl-NCD-16w (F1: n = 11; F2: n = 13; F3: n = 15; F4: n = 10); AE-NCD-16w (F1: n = 15; F2: n = 12; F3: n = 9; F4: n = 13); Ctrl-NCD-32w (F1: n = 11; F2: n = 11; F3: n = 15; F4: n = 9); AE-NCD-32w (F1: n = 10; F2: n = 14; F3: n = 10; F4: n = 11). c IPGTT of F1 male offspring at the indicated ages and the corresponding AUC of glucose levels. Ctrl (NCD-8w: n = 8; NCD-16w: n = 9; NCD-32w: n = 5; HFD-16w: n = 8); AE (NCD-8w: n = 9; NCD-16w: n = 11; NCD-32w: n = 6; HFD-16w: n = 8). d IPGTT of F2 male offspring at the indicated ages and the corresponding AUC of glucose levels. Ctrl (NCD-8w: n = 5; NCD-16w: n = 5; NCD-32w: n = 11; HFD-16w: n = 6); AE (NCD-8w: n = 5; NCD-16w: n = 5; NCD-32w: n = 12; HFD-16w: n = 6). e IPGTT of F3 male offspring at the indicated ages and the corresponding AUC of glucose levels. Ctrl (NCD-8w: n = 11; NCD-16w: n = 7; NCD-32w: n = 6; HFD-16w: n = 6); AE (NCD-8w: n = 10; NCD-16w: n = 7; NCD-32w: n = 6; HFD-16w: n = 10). f IPGTT of F4 male offspring at the indicated ages and the corresponding AUC of glucose levels. Ctrl (NCD-8w: n = 8; NCD-16w: n = 9; NCD-32w: n = 10; HFD-16w: n = 10); AE (NCD-8w: n = 8; NCD-16w: n = 12; NCD-32w: n = 9; HFD-16w: n = 9). Data are presented as mean ± SEM. *, Ctrl vs AE; statistical analyses of b, c, d, e, and f are performed using two-tailed unpaired Student’s t-test. #, AE mice at different ages; statistical analyses of b # are performed using one-way ANOVA. *P < 0.05, #P < 0.05, **P < 0.01, ##P < 0.01, ####P < 0.0001.