Effect Of Fine Particulate Matter(PM_2.5)of Wenzhou City On Pregnant Rats

BackgroundAir pollution,also known as atmospheric pollution,is usually caused by human activity or natural process.Harmful substances go into the atmosphere and endanger public health.It is going with the development of economy and has been considered as a serious social problem.Recent years,many areas come with frequent haze which regarded as a severe weather warning forecast.The "Global Environment Outlook 2000" has pointed out that air particulate matter has led to nearly 2 million death cases per year.Air pollution has been regarded as environmental carcinogens.Haze has been brought into natural disasters management for the first time in 2014,Fine particulate matter,composed of particles with an aerodynamic diameter of less than 2.5 pm(PM2.5),is composed of organic matter,sulfate,nitrate,and the earth’s crust element.There are more than 110 material composition of the organic matter of PM2.5,such as polycyclic aromatic hydrocarbons,biphenyl type of nitrogen,sulfur,and oxygen atoms.The polycyclic aromatic hydrocarbons are toxicity and can lead to macrocephaly,cancer and mutation.It can also through the placenta,combine with DNA,induce fetal DNA damage and affect fetal growth and development.Many epidemiological studies have shown that PM2.5 has a adverse effect on the public health.Inhaled PM2.5 can easily be transported from lung alveoli to capillaries,after which it is dissolved and circulated into the bloodstream via the pulmonary artery,and finally leading to different diseases.It can disturb cell physiological or biochemical process,interfere with signal transduction pathways and induce to cancer.It is associated with the increased cancer morbidity of high PM2.5 exposed groups like traffic police and road cleaners.PM2.5 may contribute to the development of chronic diseases such as diabetes,cardiovascular disease and asthma.Recent human studies revealed the decreased insulin sensitivity and increased insulin resistance under high level PM2.5 exposure.Insulin resistance,which refers to the reduced insulin sensitivity and reactivity of tissue and organs,leads to inhibition of hepatic and blood glucose and elevated blood glucose level.It is an important factor of type 2 diabetes and independent risk factors of cardiovascular complications.PM2.5 exposure can increase the body’s insulin resistance and inflammatory response.Every 10μg/m3 increased PM2.5 concentration rise 1%incidence of diabetes.Animal experiments prove that PM2.5 exposed mice show abnormal insulin resistant and body inflammatory.The glucose transporter 4 of mice skeletal muscle decreased after PM2.5 exposure.PM2.5 can promote the development of diabetes.Gestational diabetes mellitus(GDM)is regarded as a special type of diabetes which defined as carbohydrate intolerance of variable severity with onset or first recognition during pregnancy.GDM has the similar pathophysiological process to diabetes.There are 18%women worldwide develop abnormal glucose metabolism during pregnancy.Studies have found that PM2.5 is associated with glucose tolerance damage to pregnant women.Recently,epidemiological evidence has shown the association between PM2.5 exposure and adverse perinatal outcomes.Air pollutants exposure may cause abnormal embryonic damage.PM2.5 can run into utero-placental vascular system and decrease trans-placental function,with consequent pregnancy complications such as low birth weight,premature delivery,abortion and even birth defects.PM2.5 can run into maternal-fetal circulation and do harm to fetal development.As we know,adverse perinatal outcome is usually regarded as an indicator of placental dysfunction.Fetal growth is dependent on nutrient availability,which in turn is related to the placenta.This oval organ is where maternal and fetal blood are brought into very close contact,so that the mother can supply oxygen and nutrients to the fetus and remove waste products from the fetal blood at the same time.Placental insufficiency results in a variety of pregnancy complications,including abortion and fetal death.Since 2014 our experimental team has performed series of experiments to study the effect of PM2.5 on pregnant rats.To gets some clues of mechanism by which PM2.5 do harm to placenta,pancreas and perinatal outcomes,we designed and completed the following two parts experiments.Part 1 Effect of PM2.5 of Wenzhou City on Rat Placenta Pathology and Perinatal OutcomesMethods:1.PM2.5 sampling and processing.The samples of PM2.5 were collected by a particulate sampler on main traffic roads.The dry PM2.5 powder was diluted in sterile saline and kept.2.Pregnant rats model buliding.3.Pregnant rats were exposed to PM2.5(15 mg/kg)with intratracheal instillation at pregnant day 10 and day 18,while the controls received an equivalent volume normal saline.All rats received cesarean section 24 h after the last intratracheal instillation and were sacrificed with anesthesia.4.Blood routine tests(BRT)and interleukin-6(IL-6)were detected for analyzing inflammation and blood coagulation.5.The levels of placenta homogenate glutathione peroxidase(GSH-Px)and methane dicarboxylic aldehyde(MDA)were determined for oxidative stress estimation.6.Placenta tissue sections underwent pathologic examination.Results:1.Increased absorbed blastocysts,and lower maternal weight gain and fetal weight were found in the PM2.5 exposure group compared to controls(p<0.05).2.Exposure to PM2.5 caused a significant increase of blood mononuclear cells(PBMC),platelets,and IL-6 levels(P<0.01).3.There were no differences in GSH-Px and MDA of placenta homogenate between the 2 groups(P>0.05).4.Placenta pathological examination demonstrated thrombus and chorioamnionitis in the PM2.5 exposure group.Conclusions:1、PM2.5 exposure can result in placental pathological changes and adverse perinatal outcomes.2、The placental inflammation and hypercoagulability with vascular thrombosis may play important roles in placental impairment.Part 2 The effect of PM2.5 of Wenzhou City on glucose consequences and pancreas glucose transporter 2(GLUT2)expressionMethods:1.PM2.5 sampling and processing.The samples of PM2.5 were collected by a particulate sampler on main traffic roads.The dry PM2.5 powder was diluted in sterile saline and well kept.2.GDM rats model building.3.GDM rats were exposed to PM2.5(15 mg/kg)with intratracheal instillation at pregnant day 10 and day 18,while the controls received an equivalent volume normal saline.All rats received cesarean section 24 h after the last intratracheal instillation and were sacrificed with anesthesia.4.During whole exposure,maternal body weight was recorded every 3 days,as well as blood glucose which was tested by cutting off the tail tip.5.IL-6 and BRT were detected for analyzing coagulation and inflammation.6.The levels of pancreas homogenate GSH-Px and MDA were detected for oxidative stress estimation.7.The degree of GLUT2 expression of pancreas was analyzed by Western Blot.8.Pancreas tissues underwent pathologic examination.Results:1.There were lower maternal body weight gain(P<0.05)and fetal weight(P<0.01)in the PM2.5 group.2.Exposure to PM2.5 caused increased absorbed blastocyst number and higher blood mono-nuclear cells(PBMC),platelets and IL-6 levels(P<0.01).The postprandial blood glucose(PBG)was elevated at most time points after PM2.5 exposure(P<0.01).3.The pancreas of PM2.5 exposed rats revealed periductal inflammation under pathological examination.The pancreatic GSH-Px significantly reduced and MDA increased in PM2.5 exposed group(P<0.01).The pancreatic GLUTz protein expression was decreased after PM2.5 exposure(P<0.05).Conclusions:1.Our study provides direct evidence that PM2.5 exposure can result in pancreatic pathological changes,low GLUTz protein expression and high PBG level in GDM rats.2.The oxidative response and inflammation are involved in PM2.5 increased risk of pancreatic impairment and glycemic consequences.