Biphasic effect of alpha-linolenic acid on glucose-induced dysmorphogenesis and lipoperoxidation in whole rat embryo in culture

Type 1 diabetes mellitus complicated with pregnancy, know as diabetic embryopathy, is the cause of neonatal malformations and low for gestational age neonates. With the use of the whole-embryo culture system, it has been demonstrated that high glucose causes embryo dysmorphogenesis, and that oxidative stress appears to be the main mechanism. In recent years, beneficial effect of omega-3 fatty acids has been demonstrated in various diabetic models, and in diabetic complications. Since diabetic embryopathy is mediated probably through membrane lipoperoxidation, This study was designed to find if omega-3 fatty acids could ameliorate the effect of high glucose over the dysmorphogenesis of whole rat embryo in culture. Postimplantational rat embryos were cultured in hyperglycemic media, with addition of alpha-linolenic acid, and morphologic and morphometric parameters were registered. Also, lipoperoxidation and fatty acids composition were measured in cultured embryos. Growth of embryos cultured in presence of glucose was very affected, whereas lipoperoxidation was increased, and it was found that Triton X-100 causes similar results than glucose. Addition of low micromolar doses of alpha-linolenic acid overcome the effect of high glucose or Triton X-100, but higher doses does not ameliorates the effects of the carbohydrate or the detergent. Paradoxically, there are not significant changes in fatty acids composition, although the U/S fatty acids ratio shows an increasing tendency by high glucose and a normalizing tendency by omega-3 fatty acids. In conclusion, glucose and Triton X-100 induces in vitro dysmorphogenesis in post-implantational rat embryos associated with increased lipoperoxidation; and this nocive effect could be ameliorated by low micromolar doses of ALA.