| ObjectiveBy giving female rats chronic drinking water arsenic exposure during preconception and pregnant and, we discuss the relationship between the arsenic exposure and congenital heart disease. we detect of histone and gene expression of fetus heart tissue to discuss the epigenetic mechanisms, in order to provide new ideas for the research on the pathogenesis of congenital heart disease.Materials and MethodSixty SD female rats(weight 130±25 g, 30-40 days old) randomly divided into 6 groups. We have 30 male mice(weight 245±30 g). Male rats and female rats are feeding separately. The sodium arsenite diluted with distilled water. We set groups according to the concentration of Na As O2 concentration of 0 mg/L(control group), 9.4 mg/L, 18.8 mg/L, 37.5 mg/L, 75.0 mg/L, 150.0 mg/L. After feeding a week later for adaptation, female rats drink water containing different concentration of arsenic. Continuous infected 6 weeks, mice were mated overnight, and females were examined for a vaginal plug the in following morning. If a vaginal plug was observed, it was considered as embryo day 0(E0 d). The pregnant mice were given their original arsenic concentration until the E16 d. The pregnant mice were killed on E16 d. We measure pregnant rat weight every week to judge the influence on pregnant rats of arsenic exposure preliminarily. We observe embryonic form, record number of live births, dead and absorption. Placenta and embryo were weighted to assessment the embryo toxicity following drinking water sodium arsenite intake. Hematoxylin and eosin(H&E) staining was applied for observing the structure of the embryonic hearts. Western blotting and quantitative real-time polymerase chain reaction were used for detecting the level of H3K9 acetylation and heart development related genes Mef2 C m RNA expression.Result1. All the infected rats did not die, which explained that dose was appropriate.2. Sodium arsenite concentration of 75.0 mg/L and 150.0 mg/L group found 1 and 2 abortion rat respectively, that the abortion rate were 12.50 % and 22.22 % respectively. Control group and other dose infected group has not been found abortion(P<0.05).3. Compared with control group, in arsenic concentration 9.4 mg/L, 18.8 mg/L group the absorption rate has no obvious change, but with the increasing concentration of arsenic(37.5 mg/L, 75.0 mg/L, 150.0 mg/L), absorption rate increased significantly(P < 0.05).4. With increasing concentration of arsenic, number of live births per litter declined, only arsenic concentration of 150 mg/L group difference was statistically significant(P < 0.05) by One-way analysis of variance. Arsenic concentration is 18.8 mg/L, 37.5 mg/L, 75.0 mg/L, 150.0 mg/L group, fetal and placental weight were less than the control group, and with the increase of concentration fetal rats and placental weight were reduced(P < 0.05).5. Fetal hearts were not found obvious abnormality on control group and arsenic concentration 9.4 mg/L, 18.8 mg/L group. Two cases of ventricular septal defect(VSD) were found on 37.5 mg/L group. Three cases of VSD, 1 case atrial septal defects(ASD) and 1 case pulmonary artery stenosis(PS) were found on 75.0 mg/L group. Five cases VSD, 1 case of ASD and 2 cases PS were found on 150.0 mg/L group(P < 0.05).6. The level of H3AcK9 acetylation on infected group increased. What’s more, with the increase of the exposure concentration, the level was on the rise(P < 0.05).7. With the increase of concentration of arsenic, Mef2 C m RNA level gradually increased(P < 0.05), and the change trend was same as the level of H3AcK9 acetylation.ConclusionArsenic exposure during preconception and pregnancy can increase the incidence of congenital heart disease, and can produce embryo toxicity which lead to adversepregnancy outcome. It may induce cardiac tissue histone H3K9 hyperacetylation, thus increase the expression of heart development-related genes Mef2c, resulting in congenital heart disease. |
PDF Full Text Request