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 th e offspring of A/J mice subjected to surgery on day 12.5 postconceptio n (p.c.), but not in the offspring of untreated control mice. To inves tigate the cause of these defects, we compared the offspring of mice i n experimental groups involving adrenalectomy, sham adrenalectomy, blo od sampling, and anesthesia with the offspring of control mice. All tr eatments significantly reduced fetal weight and increased resorptions as compared with the controls. The highest incidence of digit anomalie s 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 clef t palate was also increased in the offspring of mice that had been sub jected to blood sampling. We conclude that digit anomalies in the offs pring of A/J mice result from fetal vascular disruptive phenomena subs equent to maternal blood loss induced hypovolemia and hypoperfusion to the uterus and placenta as has been suggested for uterine vascular cl amping, misoprostol, chorionic villus sampling, and cocaine teratogene sis. The etiology for cleft lip in these mice may involve mechanisms u nrelated to uterine/placental hypoperfusion. Teratology 58:183-189, 19 98. (C) 1998 Wiley-Liss, Inc.