Models of fetal growth restriction.

The growth of the fetus is determined by substrate supply mostly for mass accretion and energy gain, and by control systems. Experiments with whole animal models will face the following problems: (1) The fetus, like a three compartmental "Russian doll", is at the end of a long supply chain. There are interactions (e.g. hormones) and partitioning of substrates between the compartments. (2) The fetal organism is growing and differentiating at the same time and not in a steady-state. Experimental results thus depend on gestational age. (3) About 75% of animal experiments on fetal growth restriction have been performed in rats and mice. The possible experimental methods and the results depend on the species which include sheep, pigs, rabbits, guinea pigs, horses and non-human primates. Many experiments have clearly shown that restriction of substrate supply will usually impair fetal growth. Less is known about growth control mechanisms but recent studies in gene mutant mice have opened a new approach to study the effects of systemic and local controlling factors. It appears that insulin-like growth factors and their binding proteins may play an important role for fetal growth.