Effect Of Methyl Donor Or Bisphenol A Supplementation During Gestation In Sows On Intestinal Development And Function Of Offspring

Maternal nutrition intake persistently affects the growth and development of offspring via epigenetic modification way, such as changes in DNA methylation level. In this study, bisphenol A (BPA), which can induce DNA hypomethylation, was set as a negative control to explore the effects of maternal methyl donor (MET) supplementation during pregnancy on the development and function of offspring's intestine. Besides, the effect of MET on BPA induced offspring intestinal damage was explored. A total of sixty LY (Landrace×Yorkshire) sows (221.14±2.57 kg,3-5 parity) were randomly divided into four groups after breeding (n=15 per each group):1) CON group, basal diet; 2) BPA group, basal diet+bisphenol A; 3) MET group, basal diet+ methyl donor compound; 4) MET+BPA group, both bisphenol A and methyl donor compound were added into basal diet. Nutritional treatment was throughout the whole pregnancy period. All the sows were fed the same diet during lactation. Piglets were weaned at day 28 of age. At farrowing and weaning,12 newborn piglets and 6 weaning piglets, respectively close to their litter average body weight and from different sows in each group, were selected to slaughter and collect intestinal samples. The results showed that:1. Supplementation of MET in maternal diet during gestation had no effect on the average body weight and litter weight of newborn pigs, but significantly increased the average body weight and litter weight of weaning pigs (P<0.05). BPA significantly increased the average body weight and litter weight of newborn pigs (P<0.05), when the average body weight and litter weight of weaning pigs were not affected by BPA. The number of born alive and the average body weight of newborn pigs and weaning pigs were significantly influenced by the interaction of MET and BPA (P<0.05).2. Supplementation of MET in maternal diet during gestation significantly decreased the ratio of small intestine (SI) length to body weight and increased the ratio of SI weight to SI length both in newborn and weaning piglets (P< 0.05). Supplementation of BPA had a tendency to decrease the ratio of SI length to body weight in newborn piglets (P=0.06).3. Supplementation of MET in maternal diet during gestation significantly increased the ratio of villus height to crypt depth of jejunum and ileum both in newborn and weaning pigs (P<0.05). BPA significantly reduced the ratio of villus height to crypt depth of jejunum in newborn and weaning pigs (P< 0.05).The ratio of villus height to crypt depth of jejunum in newborn pigs and the ratio of villus height to crypt depth of ileum in weaning pigs were significantly influenced by the interaction of BPA and MET (P<0.05).4. Supplementation of MET in maternal diet during gestation significantly increased the gene expression and activity of jejunum lactase in newborn and weaning pigs (P<0.05), and increased the activity of duodenum and jejunum sucrase in weaning pigs (P<0.05). BPA significantly decreased the activity of jejunum sucrase in newborn pigs (P<0.05) and had a tendency to decreased the activity of jejunum sucrase in weaning pigs (P=0.07). The activity of jejunum lactase in newborn and weaning pigs were significantly affected by the interaction of MET and BPA (P<0.05).5. Supplementation of MET in maternal diet during gestation significantly up-regulated the gene expression of Peptl and Sgltl in the jejunum of newborn and weaning pigs (P<0.05). BPA significantly down-regulated the gene expression of Peptl in the jejunum of newborn and weaning pigs (P<0.05). At the same time, MET+ BPA group had a significant increase of Peptl mRNA level in the jejunum of newborn and weaning pigs compared with BPA group (P<0.05).6. Supplementation of MET in maternal diet during gestation significantly up-regulated the DNA methylation level of Peptl promoter in newborn pigs' jejunum (P <0.05), when BPA significantly decreased the DNA methylation level of Peptl promoter in newborn pigs'jejunum (P<0.05). There was no difference between CON group and MET+BPA group of the DNA methylation level of Peptl promoter in newborn pigs'jejunum.7. Supplementation of MET in maternal diet during gestation significantly increased the gene expression of jejunum DNMT1, DNMT3a and MTHFR in newborn piglets (P<0.05). BPA significantly reduced the gene expression of jejunum DNMT3a in newborn piglets (P<0.05). There was no difference between CON group and MET+BPA group of the gene expression of all the DNA methylation-related enzymes.In conclusion, supplementation of MET in maternal diet during gestation promoted the development and function of intestine in newborn and weaning pigs by improving the small intestinal index, digestive enzyme activities and the gene expression of nutrient transporter carriers. On the contrary, BPA impaired the intestinal development and function of offspring. MET could counteract the intestinal damage caused by BPA in offspring. The effect of supplementation of MET in maternal diet on offspring's intestinal development and function was associated with DNA hymethylation in the intestine.