Transuterine Puncture of the Fetal Stomach Provides Access to the Small Bowel in the Rabbit

Abstract

The prevention of perinatal complications of congenital gastrointestinal (GI) diseases such as cystic fibrosis may require prenatal treatment. New Zealand White rabbits were evaluated as a potential animal model to study gastrointestinal anatomy and transit in the fetus. The lengths of the GI tract of fetuses at 21/31 and 28/31 days gestation were established, and gastric volume was measured. Gastric volume at 28 days gestation averaged 2.6 mL, adequate to permit instillation of a solution into the fetal stomach. A study was then carried out to establish gastric emptying and delivery of the solution into the small bowel. Using ultrasound guidance, the stomachs of 26 fetuses from 7 litters were punctured and 0.5 mL of dilute barium was injected. A cesarean section was performed 4 h later and the progression of barium though the GI tract was measured. In 18/26 (69.2%) of the fetuses barium was successfully delivered to the lumen of the stomach. In these 18 fetuses, barium progressed to the duodenum in 15 (58%), the jejunum in 13 (50%), and the ileum in 8 (31%). The stomach of the 3.5- to 4-week-old fetus is large enough to allow transuterine delivery of a solution of dilute barium. Gastric and intestinal motility in the 25-day-old rabbit fetus is coordinated and results in delivery of barium to the small bowel in 50% of animals successfully injected. The results suggest that the rabbit is an acceptable model for the study of gastrointestinal delivery of therapeutic drugs or genes to the fetus.

Key Words:

• fetal
• gastrointestinal
• gene therapy