Effect of epidermal growth factor infusion on fetal rabbit intrauterine growth retardation and small intestinal development.
OBJECTIVE
Intrauterine growth retardation (IUGR) infants have impaired gastrointestinal function with resultant feeding difficulties and predisposition to necrotizing enterocolitis. Supplemented amniotic fluid swallowed by the developing fetus is a potential prenatal treatment for IUGR. Rabbits have naturally occurring IUGR fetuses based on uterine position. To determine intestinal response to epidermal growth factor (EGF) infusion, this rabbit model of IUGR was studied.


METHODS
Eight pregnant rabbits underwent placement of intraamniotic catheters into 2 normal and 2 IUGR fetuses per mother on gestational day 24 of a 31-day gestation. Miniosmotic pumps infused either EGF (about 300 microg/kg/d) or control solution forming 4 study groups (EGF-Favored [Fav] v. Cont-Fav; EGF-IUGR v. Cont-IUGR). On gestational day 31, the fetal gastrointestinal tracts were harvested for analysis. Intestinal epithelial cell proliferation was studied by 5-bromo-2-deoxyuridine (BrdU) incorporation, villus heights were measured, and EGF mRNA was measured by reverse transcriptase polymerase chain reaction (RT-PCR). Statistical analysis was performed using Students' t test.


RESULTS
Fetal survival rate was 87%. EGF-IUGR fetal weights were increased compared with Cont-IUGR fetuses. EGF infusion significantly increased IUGR fetal small intestinal villus height and BrdU-positive small intestinal (SI) crypt cells, all approaching Cont-Fav levels. EGF mRNA was expressed throughout the gastrointestinal tract.


CONCLUSIONS
Supplemental amniotic EGF normalizes fetal weight and intestinal proliferation in the IUGR fetal rabbit. The inclusion of EGF in supplemental amniotic feeding solutions is supported.
Cellini
Christina
C
Division of Pediatric Surgery, Children's Hospital of New York Presbyterian Hospital, Weill Medical College of Cornell University, New York, NY, USA.
Xu
Jian
J
Arriaga
Alexander
A
Buchmiller-Crair
Terry L
TL
D000653:Amniotic Fluid; D000818:Animals; D001724:Birth Weight / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D004815:Epidermal Growth Factor / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics / Q000627:therapeutic use*; D005260:Female; D005317:Fetal Growth Retardation / Q000188:drug therapy / Q000517:prevention & control*; D006801:Humans; D015918:Infusion Pumps, Implantable; D007421:Intestine, Small / Q000196:embryology*; D011247:Pregnancy; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011817:Rabbits; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use
D012333:RNA, Messenger; D011994:Recombinant Proteins; D004815:Epidermal Growth Factor