Intrauterine growth restriction in a rodent model and developmental programming of the metabolic syndrome: a critical appraisal of the experimental evidence.
Research on intrauterine growth restriction (IUGR) and subsequent development of obesity, type 2 diabetes and the metabolic syndrome is rapidly expanding, and potential implications for primary prevention are considerable. We have critically appraised one of the experimental animal models frequently used as mimic of human fetal growth restriction, which involves bilateral ligation of the uterine artery in rats (Lig). Our experimental study showed that Lig performed on day 17 of pregnancy neither leads to IUGR nor to neonatal catch-up growth, an important pathogenetic co-factor in humans. Meta-analysis of the literature revealed domination by studies in which Lig pups with IUGR were actively selected. Accordingly, publication bias is evident (p=0.007). Altered placental perfusion--the main cause of IUGR in humans in Western countries--neither led to IUGR nor to neonatal catch-up growth in Lig offspring, i.e., to none of the etiological factors of the human 'small baby syndrome'. Appropriate and reproducible rodent models of IUGR through decreased placental flow remain to be established to uncover the pathophysiological basis of the 'small baby syndrome'. This may lead to new strategies of primary prevention of diabetes, obesity, and the metabolic syndrome.
Neitzke
U
U
Clinic of Obstetrics, Research Group Experimental Obstetrics, Charité-University Medicine Berlin, Campus Virchow-Klinikum, Augustenburger Platz 1, Berlin, Germany.
Harder
T
T
Schellong
K
K
Melchior
K
K
Ziska
T
T
Rodekamp
E
E
Dudenhausen
J W
JW
Plagemann
A
A
D000465:Algorithms; D000818:Animals; D000831:Animals, Newborn; D001158:Arteries / Q000601:surgery; D001724:Birth Weight; D005260:Female; D005317:Fetal Growth Retardation / Q000473:pathology*; D005333:Fetus / Q000098:blood supply / Q000378:metabolism; D008026:Ligation; D008297:Male; D024821:Metabolic Syndrome / Q000196:embryology*; D023421:Models, Animal; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D014599:Uterus / Q000098:blood supply