No abstract

This study investigated the effects of homocystine diet and folate supplementation on the alteration of homocysteine metabolism and DNA methylation in the rat placenta during pregnancy. Female SD rats were divided 3 diet groups (F: 8 mg/kg folic acid, H: 0.3 % homocystine and 0 mg folic acid, HF: 0.3 % homocystine and 8 mg/kg folic acid). They were fed experimental diets for 5 wks prior to the mating and also during the entire period of pregnancy till gestational d 20. Folic acid supplementation caused a significant decrease in plasma homocysteine levels which had been increased by a homocystine‐diet, with a concomitant increase in plasma, liver, and placenta folate levels. The placental SAM level was significantly increased by the folate supplementation compared to the animal fed a folate deficient homocystine diet. Also, folate supplementation caused a significant increase the SAM/SAH ratio which had been decreased by a homocystine‐diet in the liver and placenta. We found a significant increase of global DNA methylation in the placenta by folate supplementation. The negative correlations were observed between plasma homocysteine and placental levels of folate (r=−0.756, p<0.001), SAM (r=−0.659, p<0.05), and SAM/SAH ratio (r=−0.534, p<0.001). Thus, folate supplementation to the hyperhomocysteinemic pregnant rats might prevent the alteration of homocysteine metabolism and DNA methylation in the placenta.