The induction of congenital spinal deformities in mice by maternal carbon monoxide exposure.

Carbon monoxide (CO) has been shown to be teratogenic in mice. High altitude hypoxia has also been shown to induce congenital vertebral anomalies in mice. The purpose of this study was to investigate the effect of maternal hypoxia owing to CO exposure and the production of congenital spinal deformities in the offspring. Sixty DBA-1J mice were bred using polygamous timed breeding methods. Pregnant females were exposed to 200, 400, or 600 ppm CO using a custom-designed gas blender system. Seven-hour exposures were performed on day 8.5, 9.5, or 10.5 of the 21-day gestation cycle. The neonates were euthanized at birth; the specimens were fixed, eviscerated, and radiographed. Congenital spinal deformities were observed (wedge, hemi, fused, and missing vertebrae; fused ribs) and were located in all regions of the spine. There was a statistically significant difference in the number of spinal deformities between all groups, with no defects in the controls and a 77% incidence at 600 ppm (p < 0.0001). There was no apparent correlation between the time of exposure and defect location. The most sensitive time of gestation was 9.5 days. We identified an animal model of congenital spinal deformities that compares favorably with the evidence of human congenital spinal deformities in cases of maternal exposure to CO and other gas and chemical fumes.

Are regional variations in bone growth related to mechanical stress and strain parameters?

A three-dimensional finite element analysis was used to quantify the patterns of mechanical stresses within the rabbit distal femur growth plate, and test the hypothesis that these patterns are correlated to measured patterns of bone growth rates. This investigation of normal development is the first step toward improving our understanding of the role of mechanical factors in bone growth abnormalities. Rabbits from five age groups ranging from 1 to 42 days were evaluated, and four different loading conditions were analyzed, representing specific time points in the normal gait cycle. Finite element models generated directly from micro-computed tomography images of the distal femurs identified regional variations in stress and strain parameters, similar to the variations in bone growth rates measured using fluorochrome labeling. A linear regression analysis supports the hypothesis that high compressive stresses are correlated with lower bone growth rates. However, for the loading conditions considered in this study, the variations in mechanical stress and strain parameters explain no more than 15% of the overall variations in bone growth rates. The greatest variations in both growth rates and mechanical stresses were present in the anterior frontal plane from the 42 day age group, in which correlations between reduced bone growth rates and compressive stresses were much stronger (r2 up to 0.80).

Muscle and tendon size relationships in a paralyzed chick embryo model of clubfoot.

Clubfoot is a birth defect that may be related to muscle weakness or imbalance. The purpose of this study was to examine the relationships among muscle and tendon size and embryonic motility in a paralyzed chick embryo model of clubfoot and arthrogryposis. Decamethonium bromide, a neuromuscular blocking agent, was administered to a series of embryos in five dosage groups, producing a cohort of embryos with various degrees of paralysis and atrophy of tendons and muscle. Embryonic movement frequency was monitored, and after death in late gestation, the cross-sectional areas of the calf musculature and the gastrocnemius tendon proximal to the ankle were measured histologically. Significant correlations were found between embryonic motility and both muscle (r2 = 0.52) and tendon (r2 = 0.77) areas. In addition, a significant correlation (r2 = 0.74) was found between muscle and tendon areas, suggesting that a measurement of one may be used to predict the other.

Characterization of regional and age-related variations in the growth of the rabbit distal femur.

Fluorochrome labeling and microcomputed tomography were used to completely characterize the regional and age-related variations in bone growth in the distal femur of the young rabbit. Use of the microcomputed tomography system, in conjunction with the more routine fluorochrome labeling, allows the investigation of changes in shape that occur during development. The growth plate in the distal femur studied here is remarkable for several reasons. First, growth rates of as much as 700 microns/day were measured, a much higher rate than those typically measured in other species or in more mature animals. In addition, regional variations in bone growth rates of as much as 300 microns/day were identified in the 6-week-old rabbit. These variations resulted in the formation of a complex curvature in the growth plate, including four mammillary processes. Identifying the factors that regulate this type of regional variation may be especially useful in understanding the causes for angular deformities such as tibia vara or developmental dysplasias.