Dimethyl Fumarate Alleviates Oxidative Damage of Fine Particulate Matter to the Placenta of Female Rats through the Nrf2/HO-1 Signaling Pathway
In recent years,a large number of epidemiological investigations have confirmed that maternal exposure to PM2.5 may increase the risk of pregnancy complications and adverse pregnancy outcomes.The aim of this study is to investigate the damage of PM2.5 exposure before pregnancy to the placenta of rats and the underlying regulatory mechanism of dimethyl fumarate(DMF).Forty 6-week-old SPF grade fe-male SD rats were randomly divided into the control group(normal saline),the low-dose PM2.5 group(1.5 mg/kg PM2.5),the high-dose PM2.5 group(7.5 mg/kg PM2.5),a DMF control group(normal sa-line+50 mg/kg DMF),and the DMF intervention group(7.5 mg/kg PM2.5+50 mg/kg DMF).Rats were exposed to PM2.5 once every two days for a total of a 40 day period.After exposure to PM2.5,the number and average body length of fetuses in the high-dose PM2.5 group were significantly lower than those in the control group(P<0.05),as well as the activity of superoxide dismutase(SOD),total an-tioxidant capacity(T-AOC)and the concentration of interleukin-10(IL-10)in placental tissues in the high-dose PM2.5 group were significantly lower than those in the control group(P<0.05),while the content of malondialdehyde(MDA)was higher than that in the control group(P<0.05).After the DMF treatment,the T-AOC in the DMF intervention group was significantly higher than that in the high-dose PM2.5 group(P<0.01),this suggested that DMF treatment might alleviate the oxidative damage induced by PM2.5.The H&E staining results of rat placental tissues showed that there was a varying de-gree of reduction in the number of blood cells in the labyrinthine area of the PM2.5 exposure group.The high-dose PM2.5 group had unclear vascular choroids,while the DMF intervention group had a significant increase in the number of blood cells in the labyrinthine area of the placenta and had clear vascular cho-roids.Western blotting results showed that the protein levels of nuclear factor E2 related factor(Nrf2)and heme oxygenase-1(HO-1)in the low-dose PM2.5 group and high-dose PM2.5 group were lower than those in the control group(P<0.01).Compared with the high-dose PM2.5 group,the protein level of Nrf2 and HO-1 in the DMF intervention group was significantly increased(P<0.05).In summary,DMF may alleviate the oxidative damage to the placenta caused by PM2.5 exposure before pregnancy and improve the body antioxidant capacity through the Nrf2/HO-1 signaling pathway.