Fetal therapy with rhIGF-1 in a rabbit model of intrauterine growth retardation.
BACKGROUND
Intrauterine growth retardation (IUGR) may, in part, be due to a deficiency of insulin-like growth factor-1 (IGF-1). The objectives of this study were to determine the relationship between fetal serum IGF-1 levels and fetal and placental size in a rabbit model of IUGR and to compare two techniques of selective, exogenous IGF-1 administration (transamniotic and branch uterine arterial catheter infusion) to growth-retarded fetuses in utero.


METHODS
Pregnant rabbits (n = 6) had their fetuses harvested near term (31 days) for fetal and placental weighing and serum collection. Growth-retarded fetuses were selectively infused for 7 days with recombinant human IGF-1 (rhIGF-1; 1,440 ng/day) either through a transamniotic catheter (n = 8) or via an adjacent uterine arterial branch catheter (n = 6). Opposite horn runts were sham catheterized, but not infused. At term, the fetal runt pairs and their placentas were harvested and weighed, and their serum was collected. The correlation between fetal and placental weight and endogenous serum IGF-1 was calculated (Pearson coefficient, r), while paired t-tests were used to compare the means between the IGF-1-infused and control groups.


RESULTS
There was a significant correlation between fetal (r = 0.4230; P = 0.022) and placental weight (r = 0.4166; P = 0.025) and endogenous serum levels of IGF-1. Transamniotic infusion of rhIGF-1 was associated with an increase in serum IGF-1 level (254 +/- 79 vs 351 +/- 101 ng/ml, P = 0.04) and placental weight (5.4 +/- 2.3 vs 7.1 +/- 3.2 g, P = 0.005), and with a trend toward increased fetal weight between matched fetal runt pairs. Fetal mortality in the uterine arterial catheterized group was 76%, and there was no significant difference in fetal or placental weight or IGF-1 levels between infused and noninfused survivors.


CONCLUSIONS
Endogenous fetal serum levels correlate with fetal and placental size in the rabbit IUGR model. Transamniotic administration of rhIGF-1 significantly increases serum IGF-1 levels and placental weight of fetal runts, while uterine vessel catheterization results in prohibitive fetal mortality and does not increase fetal or placental growth or IGF-1 levels.
Skarsgard
E D
ED
Department of Surgery, Lucile Packard Children's Hospital, Palo Alto, California 94025, USA. erik.skarsgard@medcenter.stanford.edu
Amii
L A
LA
Dimmitt
R A
RA
Sakamoto
G
G
Brindle
M E
ME
Moss
R L
RL
D000650:Amnion; D000818:Animals; D002404:Catheterization / Q000401:mortality; D005260:Female; D005312:Fetal Blood / Q000378:metabolism; D005313:Fetal Death; D005317:Fetal Growth Retardation / Q000188:drug therapy*; D006801:Humans; D007267:Injections; D007269:Injections, Intra-Arterial; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D009929:Organ Size / Q000187:drug effects; D010920:Placenta / Q000033:anatomy & histology; D011247:Pregnancy; D011817:Rabbits; D011994:Recombinant Proteins; D014599:Uterus / Q000098:blood supply
D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I