Cooking Oil Fumes-derived Fine Particulate Matter Result In Intra-uterine Growth Restriction Through Injury Of Umbilical Cord Blood Vessels

Purpose In order to observe the influence of exposure of cooking oil fumes(COFs)-derived fine particulate matter(PM2.5) on the growth and development of offspring rats and the injury of blood vessels in umbilical cord and explore the explicit mechanism of impact, we prepared a rat model within exposure of COFs-derived PM2.5. Besides, we establish an umbilical cord exposed model in vitro to further explore the mechanism.Methods 1、40 pregnant SD rats were divided into 5 groups,(1) the control group, injection of saline solution within tail vein;(2) pre-pregnant injected group: tail intravenous injection of COFs-PM2.5 2w before pregnancy(0.5 mg/ml);(3) low-dose injected group in the early stages of pregnancy: tail intravenous injection of COFs-PM2.5 from GD1 to GD8(0.5 mg/ml);(4) high-dose injected group in the early stages of pregnancy: tail intravenous injection of COFs-PM2.5 from GD1 to GD8(1.0 mg/ml);(5) pregnant infected group: low-dose injected group in the early stages of pregnancy: tail intravenous injection of COFs-PM2.5 from GD1 to GD20(0.5 mg/ml). The rats were feed with normal diet and infected once 1 day. The rats were executed at GD21, and the pregnancy outcome and the growth and development situation were measured, such as the body length, tail length and body weight. Each viscera were separated and weighed. The umbilical cord blood vessels were also collected. HE staining and scanning electron microscope(SEM) were used to examine the damage ofumbilical cord blood vessel. The umbilical cord vascular ring was prepared to detect the vasomotor function. We also detected levels of oxidative stress and inflammation. Besides, related protein expression in umbilical cord blood vessels were measured with Western Blot and immune histochemical method analysis. 2、Umbilical cord blood vessels were extracted from 10 pregnant SD rats at GD21, and divided into 4 groups:(1) the control group(saline);(2) low dose group(0.25 mg/ml);(3) middle dose group(0.50 mg/ml);(4) high dose group(1.0 mg/ml). The blood vessels were exposed to COFs-derived PM2.5 for 2h. After exposure, the blood vessels were used for vascular ring experiment to detect vasomotor function. We also detected levels of oxidative stress and inflammation. Besides, related protein expression in umbilical cord blood vessels were measured with Western Blot.Results 1. Exposure of COFs-derived PM2.5 within different time and dose resulted in intra-uterine growth restriction(IUGR). Compared to the control group, the weight of fetal rats in high-dose injected group and pregnant infected group were decreased significantly(p<0.05), number of live births and weight gain during pregnancy were also decreased significantly(p<0.05). However, number of stillbirths and some important organs(heart, brain, lung) organ coefficient increased(p< 0.05). 2. Exposure of COFs-derived PM2.5 within different time and dose resulted in injury of umbilical cord blood vessels. Compared to the control group, the structure of umbilical cord blood vessels in high-dose injected group and pregnant infected group were changed significantly. Under light microscope, the diameter and lumen area were significantly decreased. However, the wall thickness was increased. The endothelium was incomplete and out of shape, a few mononuclear cells infiltrated, and the smooth muscle cells expanded. Under electron microscope, the endothelial cells and smooth muscle cells expanded obviously, mitochondria membrane fused, organelles losed, and local necrosis. 3. Exposure of COFs-derived PM2.5 within different time and doseresulted in injury of umbilical cord blood vessels. Compared to the control group, the vasomotor function of umbilical cord blood vessels in high-dose injected group and pregnant infected group were decreased significantly. Furthermore, detection of NO and ET-1 demonstrated that they were decreased and increased, respectively. 4. Exposure of COFs-derived PM2.5 within different time and dose resulted in increase of oxidative stress and inflammation. Compared to the control group, the ROS level, TNF-α and IL-6 level of umbilical cord blood vessels in high-dose injected group and pregnant infected group were increased significantly. However, levels of total-SOD and Cu Zn-SOD were significantly decreased. 5. Exposure of COFs-derived PM2.5 within different time and dose resulted in change of e NOS, p-e NOS, ETRA, and ETRB expression. Compared to the control group, ETRA and ETRB expression of umbilical cord blood vessels in high-dose injected group and pregnant infected group were increased significantly. However, e NOS and p-e NOS expression of umbilical cord blood vessels in high-dose injected group and pregnant infected group were significantly decreased. 6. Exposure of COFs-derived PM2.5 within different time and dose resulted in change of HIF-1αand VEGF/VEGFR1 expression. Compared to the control group, HIF-1αand VEGF/VEGFR1 expression of umbilical cord blood vessels in high-dose injected group and pregnant infected group were increased significantly.Conclusion Exposure of COFs-derived PM2.5 within different time and dose resulted in increase of oxidative stress and inflammation and injured the vasomotor function of umbilical cord blood vessels. Furthermore, Exposure of COFs-derived PM2.5 might affect the transportation of nutrition and oxygen, which might result in IUGR in fetus.