HISTOLOGICAL ANALYSIS OF LIMB DEFECTS INDUCED IN DEVELOPING LIMB BUDSOF NMRI MOUSE EMBRYOS AFTER ORAL-ADMINISTRATION OF 3-3-DIMETHYL-1-PHENYLTRIAZENE (DMPT) TO THEIR MOTHER ON DAY 10 OF GESTATION

A single oral dose of DMPT was given to pregnant NMRI mice on day 10 o f gestation and the subsequent histological changes were studied in se rial sections of affected limb buds isolated from 13-, 12- and 11-day treated embryos. Differences in abnormal skeletal patterns observed be tween fore- and hindlimb buds as well as between embryos from differen t litters provided clear evidence that the teratogen hits preferential ly undifferentiated preskeletal mesoderm just before blastema formatio n. Absence or severe reduction of skeletal rudiments characterizes sel ectively the girdle and stylopod of hindlimbs and the zeugopod and aut opod in forelimbs. In embryos slightly more advanced at the time of dr ug administration, the defects shifted in the zeugopod and distal segm ent of the posterior limb and in the distal segment only of the anteri or limbs. In all cases, defects in the two distal segments displayed a postaxial predominance. Extensive cell death detected in the undiffer entiated mesoderm of the affected limb parts of 11-day embryos similar ly exhibited a postaxial predominance with the maximal damage in the Z PA territory. Together with the regular genesis of a postaxial subecto dermal bleb in that area, followed by local involution of the AER, thi s observation strongly suggests that the teratogenic injury might invo lve an early impairment of ZPA and AER properties. In addition, predic tive signs of hyperphalangy of digit I and distal duplication of the I Id to e could be correlated with a transient reactional hyperplasia re stricted to the preaxial part of the AER.