Validation of an experimental model of fetal limb growth and development: Practical applications for the study of fetal defects associated with therapeutic agents in pregnant women

Numerous musculoskeletal disorders which occur during pregnancy require an effective, nonpharmacological treatment that is known to have no adverse effects on fetal development. The present report describes morphological and histological changes occurring in fetal mouse limbs maintained in a serum-free organ culture system. Limbs maintained in this organ culture system show a progressive rise in limb dimensions including surface area, perimeter, and limb length. Histological analysis of serial cross sections of the limbs revealed a statistically significant increase in histological scores of limb development, thickness of epidermal layer, and amount of collagen deposited in the bone and dermis of limbs by Day 4 of culture. Therefore, this in vitro model combined with contemporary computer image analysis represents an excellent experimental model which can be used readily to examine the effects of therapeutic modalities on the growth and development of many different organ systems.