Restraint-induced stress in pregnant mice--degree of immobilization affects maternal indices of stress and developmental outcome in offspring.

Maternal stress on gestational day 8 (GD8) in the CD-1 mouse can induce a syndrome of fetal anomalies, including encephalocele, supernumerary ribs, fused ribs and vertebral anomalies. Two forms of restraint were compared for their ability to induce these defects. The two types of restraint differed in the degree of mobility afforded the dam during confinement, either total restraint in a supine position or a less confining restraint in which restrained dams could move from a supine to a non-supine position, but could not turn from front to back. Dams were exposed to either form of restraint for 12 h on GD8 and their near-term fetuses examined for external and skeletal abnormalities. As both types of restraint precluded normal eating and drinking, an additional control group deprived of food/water was included for evaluation. Cohorts of dams were restrained for 3, 6 or 12 h on GD8 and end points commonly used to gauge the degree of stress evaluated. These included serum corticosterone level and the weight of body, spleen and thymus. Stress-induced analgesia, as measured by the tail-flick procedure, was monitored in these same dams as an additional non-invasive measure of stress. Both types of restraint induced greater and longer-lasting weight loss than food/water deprivation. Both also produced more fetal anomalies than observed in the offspring of caged controls or food/water deprived dams. Both forms of restraint equally elevated serum corticosterone levels above the increase exhibited by the food/water deprived dams. The most pronounced difference between the two types of restraint concerned the degree of analgesia. The type limiting mobility the most, caused much greater analgesia after 6 and 12 h of restraint although the dams subjected to the other form of restraint were significantly more analgesic than the food/water deprived dams by 12 h. Dams restrained in the supine position exhibited slightly greater weight loss, more analgesia and produced significantly more offspring with anomalies.