Pathogenesis of retinoic acid-induced abnormal pad patterns on mouse volar skin

Background: Abnormal dermatoglyphs on human volar skin have been reported in many syndromes, but little is known about the pathogenesis. Patterns of pads on rodent limb volar skin are homologous to human dermatoglyphs. Methods: In previous studies, we showed that transplacental exposure to teratogens induced abnormal pads in mouse fetuses. Moreover, teratogens caused abnormal pad patterns at levels below those that caused skeletal malformations. In this study, we examined morphology and cytokinetics in developing abnormal pads. Pregnant mice were treated with all-trans-retinoic acid at 20 mg/kg orally at embryonal day (E) 12.5 (vaginal plug = E0). The hindlimbs of the embryos were harvested and observed under a light microscope and by scanning electron microscopy. Cell proliferation and cell death were estimated by 5-bromo-2'-deoxyuridine (BrdU) labeling, Nile blue A vital staining, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). Results: Retinoic acid induced aplasia of the fibular tarsal pad and supernumerary interdigital pads on hindlimbs. Cell proliferation was observed in the area of developing pad, but cell death was very rarely seen in either normal or abnormal pads. Conclusions: Retinoic acid disturbed pad patterning as a whole rather than individual pad formation.