Failure of short-term luminal IGF-I to protect against atrophy in a model of fetal esophageal atresia.

ABSTRACT

Short-term luminal infusion in utero (3 days) of insulin-like growth factor I (IGF-I) failed to protect the fetal small intestine against atrophy induced by ablation of swallowing. Human recombinant IGF-1 (or vehicle) was infused into the duodenum of fetal sheep at 125 days' gestation for 3 days (day 1, 0.025 mg; day 2, 0.25 mg day 3, 2.5 mg). Fetal swallowing was prevented by esophageal ligation, and a carotid catheter was implanted for blood sampling. There were no changes in body growth of in major organ growth. Small intestinal (SI) weight (corrected for body weight) was significantly lower for IGF-I treated fetuses. Villus height decreased significantly in proximal regions. Villus enterocyte cellularity was reduced significantly in the proximal regions. The percentage of crypt cells labeled with a 4-hour pulse of tritiated thymidine (as assessed by autoradiography) decreased significantly in the proximal SI only, from 16.14% (1.06% SEM) to 13.28% (1.05% SEM) (P < .05). Plasma levels of IGF-1 increased in the treated fetuses by an average of 76%. IGF-1 immunoreactivity was detected in the apical endocytic complex of enterocytes from proximal SI. This study shows that wasting of fetal intestinal tissues in the absence of enteral input cannot be prevented by IGF-1 delivered luminally.