Abstract

    The present study was conducted to evaluate the effect of caffeine and retinoic acid either in separate or in combination on the skeleton of the developing embryos of mice. Pregnant females were treated with either caffeine or retinoic acid at the onset of organogenesis (7th day of gestation). At morphological level no abnormalities in either caffeine or retinoic acid in the developing embryos at 14th day of gestation whose mother's administered caffeine (2 mg/100g b.w.) or those of the mother's treated with retinoic acid up to  4mg/kg b.w. during the onset of the second trimester of pregnancy were observed. However, dose-dependent retinoic acid treatment initiate chondrocyte vacuolation, depression of PAS+ve intracellular inclusions  and depression of nuclear fluorescence that concomitant with dowenregulation of TGFβ2 expression in the perichondrium of the developing vertebrae. Co-administration of caffeine was found to ameliorate the effects of 2 mg/kg b.w. rather than 4 mg/kg b.w. of retinoic acid treatment. At 18th day of gestation the uterine horns appeared normal without any signs of foetoresorption in all treatments. However, the effect of both caffeine (2 mg/100g b.w) and retinoic acid at both doses (2, 4  mg/kg b.w ) in Alizarin Red stain of wholemount revealed minor phalanges deformation of the developing limbs either in separate or in combined treatments.