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.

Prenatal Orogastric Gene Delivery Results in Transduction of the Small Bowel in the Fetal Rabbit

“…By 22 weeks' gestation, the intestinal tract is histologically normal, with increasing secretion of mucus as well as increasing coordination of peristalsis [15]. Although difficult to objectively measure, the amount of mucus seen in the fetal intestine appears to be decreased when compared to newborn or adult controls, which theoretically could improve transduction with viral vectors [13,[16][17][18]. The development of peristalsis of the GI tract in the perinatal period has been extensively studied, because of the clinical relevance of the feeding of preterm infants [19,20].…”

“…The rabbit, however, is a well-recognized model for fetal surgery [11,12]. The rabbit fetal stomach is large enough to allow delivery of fluids, and peristalsis in the GI tract of the 3-week rabbit fetus is developed enough to deliver gastric contents to the small bowel [13].…”