Amniotic IGF-I supplements improve gut growth but reduce circulating IGF-I in growth-restricted fetal sheep.
Insulin-like growth factor I (IGF-I) is an important regulator of fetal growth, and circulating concentrations are reduced in intrauterine growth-restricted (IUGR) fetuses. We investigated whether IGF-I administered into amniotic fluid could ameliorate IUGR in fetal sheep. Fetuses were assigned to control (n = 9), IUGR+saline (n = 12), or IUGR+IGF-I groups (daily intra-amniotic IGF-I injections of 20 microg, n = 13). IUGR was induced by placental embolization from 114 to 120 days. Treatment was from 120 to 130 days of gestation. Embolization produced asymmetrically IUGR fetuses with decreased body weight and lighter, thinner-walled guts. Fetal plasma and amniotic IGF-I levels were reduced. During treatment, fetal plasma, but not amniotic, IGF-I levels recovered in the saline group but remained depressed in the IGF-I-treated group. IGF-I treatment restored gut weight and wall thickness to control levels and increased the number of crypt mitoses. Fetal weight was similar to that of controls, but spleen, liver, and thymic weights were reduced by 30-37%, and placentome growth was altered. Amniotic fluid IGF-I supplementation may provide the basis of future therapeutic approaches to IUGR, but the systemic effects require further investigation.
Bloomfield
Frank H
FH
Liggins Institute, University of Auckland, Private Bag 92019, Auckland, New Zealand.
Bauer
Michael K
MK
van Zijl
Pierre L
PL
Gluckman
Peter D
PD
Harding
Jane E
JE
D000653:Amniotic Fluid / Q000378:metabolism*; D000818:Animals; D005314:Embryonic and Fetal Development / Q000187:drug effects; D004798:Enzymes / Q000378:metabolism; D005260:Female; D005312:Fetal Blood / Q000378:metabolism*; D005317:Fetal Growth Retardation / Q000188:drug therapy* / Q000196:embryology*; D005333:Fetus / Q000033:anatomy & histology / Q000378:metabolism; D007267:Injections; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D007413:Intestinal Mucosa / Q000196:embryology; D007422:Intestines / Q000196:embryology* / Q000473:pathology; D010920:Placenta / Q000187:drug effects; D010929:Placentation; D011247:Pregnancy; D012756:Sheep / Q000196:embryology
D004798:Enzymes; D007334:Insulin-Like Growth Factor I