Fig. 2. Enteral administration of retinoic acid attenuates the effect of necrotizing enterocolitis by preventing the induction of apoptosis of crypt-based intestinal stem cells.

A, confocal images of TUNEL stained sections of the terminal ileum obtained from control mice that did not (i and v) or did (iii and vii) receive ATRA (50 μg/mouse orally per day) and mice submitted to experimental NEC in the absence (ii and vi) or presence (iv and viii) of ATRA. The outlined areas in i – iv are shown at a higher magnification in v – viii. Apoptotic cells within the crypts are identified by arrows and demonstrate the significant effect that ATRA has on the induction of NEC by preventing cell death within the ISC population. B, TUNEL staining intensity was quantified as described in the methods section and expressed as a percentage of the total number of cells identified within the crypts per high-magnification field. Scale bar = 50μm. Data depicted is presented as mean ± SD and represents 3 independent experiments with at least 10 mice per group. ***P ≤ 0.0001 determined by ANOVA followed by Tukey's multiple comparisons.