Effect of esophageal ligation on small intestinal development in normal and growth-retarded fetal rabbits

Objective: The uninterrupted passage of amniotic fluid through the gastrointestinal tract is hypothesized to influence both intestinal and overall fetal somatic development. The effect of in utero esophageal ligation (EL) and therefore the exclusion of AF on somatic growth, small intestinal (SI) morphology and proliferation, and the expression of the glucose transporter sodium-glucose cotransporter 1 (SGLT-1) in both normal and intrauterine growth-retarded (IUGR) fetal rabbits were evaluated. Methods: Thirteen pregnant New Zealand white rabbits underwent surgery on day 24 of their normal 31-day gestation. Ipsilateral normal and fUGR fetuses underwent EL; the contralateral normal and IUGR fetuses underwent cervical exploration only forming 4 study groups (control-normal, control-IUGR. EL-normal and EL-IUGR). Rabbits were killed on day 31. Small intestinal villus height was measured, and epithelial cell proliferation was determined by proliferating cell nuclear antigen staining. Sodium-glucose cotransporter 1 messenger RNA (mRNA) and protein expressions were analyzed. Statistical analysis was performed using 2-way analysis of variance. Results: Esophageal ligation reduced fetal weight in IUGR by 15% and in normal by 10%. Villus height was significantly reduced in IUGR versus normal in both control and EL (control, P = 0.01; EL, P = 0.05). Intrauterine growth-retarded fetuses had reduced SI proliferation versus normal in both control and EL. Sodium-glucose cotransporter 1 mRNA production in EL fetuses was equal to control fetuses. Esophageal ligation-normal and EL-IUGR fetuses exhibited reduced protein levels and decreased staining for SGLT-1 in villus enterocytes. Conclusions: Amniotic fluid exclusion by in utero EL reduced fetal weight. Small intestinal proliferation was not affected by EL. Although SGLT-1 mRNA and protein were produced in all 4 groups, exposure of the fetal gastrointestinal tract to amniotic fluid appears necessary for proper brush border expression of nutrient transporter proteins.