Limb reduction defects in the A/J mouse strain associated with maternal blood loss.

We previously described a high incidence of digit/limb anomalies in the offspring of A/J mice subjected to surgery on day 12.5 postconception (p.c.), but not in the offspring of untreated control mice. To investigate the cause of these defects, we compared the offspring of mice in experimental groups involving adrenalectomy, sham adrenalectomy, blood sampling, and anesthesia with the offspring of control mice. All treatments significantly reduced fetal weight and increased resorptions as compared with the controls. The highest incidence of digit anomalies occurred in the offspring of dams from which blood samples had been drawn on days 12.5, 14.5, and 15.5 p.c. The incidence of isolated cleft palate was also increased in the offspring of mice that had been subjected to blood sampling. We conclude that digit anomalies in the offspring of A/J mice result from fetal vascular disruptive phenomena subsequent to maternal blood loss induced hypovolemia and hypoperfusion to the uterus and placenta as has been suggested for uterine vascular clamping, misoprostol, chorionic villus sampling, and cocaine teratogenesis. The etiology for cleft lip in these mice may involve mechanisms unrelated to uterine/placental hypoperfusion.