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

• Published in: Journal of pediatric surgery Vol. 30; no. 11; pp. 1564 - 1570
• Main Authors: Trahair, Jeff F., Wing, Sarah J., Horn, Julie L.
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA Elsevier Inc 01-11-1995; Elsevier
• Subjects: Animals; Atrophy; Biological and medical sciences; Biological Transport; Cell Division; Deglutition - physiology; Disease Models, Animal; Embryonic and Fetal Development - drug effects; Esophageal Atresia - complications; Esophageal Atresia - embryology; Esophageal Atresia - prevention & control; Gastroenterology. Liver. Pancreas. Abdomen; Insulin-Like Growth Factor I - metabolism; Insulin-Like Growth Factor I - pharmacology; Intestinal Mucosa - drug effects; Intestinal Mucosa - embryology; Intestinal Mucosa - immunology; Intestinal Mucosa - ultrastructure; Intestine, Small - drug effects; Intestine, Small - embryology; Intestine, Small - immunology; Intestine, Small - ultrastructure; Medical sciences; Other diseases. Semiology; Sheep; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Thymidine - metabolism; tritiated thymidine; IGF-I; small intestine; cell proliferation; fetus; Insulin like growth factor 1; In utero; Small intestine; Esophagus; Vertebrata; Experimental disease; Mammalia; Treatment; Malformation; Perfusion; Animal; Atrophia; Atresia; Digestive diseases; Complication; Sheep; Artiodactyla; Ungulata
• ISSN: 0022-3468; 1531-5037
• DOI: 10.1016/0022-3468(95)90158-2

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-I (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 or 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-I increased in the treated fetuses by an average of 76%. IGF-I 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-I delivered luminally.