孕期暴露于空气污染物可引起不良妊娠结局，组织缺氧和表观遗传改变是产生不良妊娠结局的关键。镍是常见的污染物，可引起组织缺氧和表观遗传改变，能否引起不良妊娠结局？本研究拟在甘肃两个空气镍浓度相差84倍的城市各选择200名孕妇，于孕13、25、35周和生产时采集孕妇血和尿、胎儿脐带血，测量胎儿BPD、OFD、HC、FL和AC，新生儿体重、身长和头围；分析母血及脐带血镍浓度；测定脐带血VEGF、ANGTPL4、血脂、CRP、IL-6、8-异前列腺素、3-硝基酪氨酸、8-羟基脱氧鸟苷，HIF-1α、Alu-1、LINE-1、H3K4三甲基化和H3K9二甲基化。探讨①胎盘屏障能否有效阻止镍从母体转运至胎儿；②产前镍暴露能否减缓胎儿生长发育；③产前镍暴露能否影响胎儿心血管系统发育或引起脂类代谢紊乱；④胎儿摄取的镍是否引起DNA甲基化和组蛋白修饰；⑤镍引起的氧化应激和炎性反应是不是造成胎儿不良作用的原因。

Maternal exposure to ambient air pollutants during pregnancy plays a critical role in causing adverse pregnancy outcomes. Hypoxia and epigenetic alterations are critical for adverse pregnancy outcomes. Nickel (Ni) is a widespread environmental pollutant, it can induce hypoxia and epigenetic alterations, whether can it cause adverse pregnancy outcomes? We will recruit 200 nonsmoking pregnant women in each city that the ambient levels of Ni are different more than 84 fold between two cities, and fetal growth and development will be assessed by ultrasound measurements at different time periods of gestation for biparietal diameter, occipital frontal diameter, head circumference, femur length, and abdominal circumference, their blood, urea and cord blood will be collected and VEGF, ANGPTL4 protein, and Lipid Profile,CRP,IL-6,8-Isoprostane,3-Nitrotyrosine,and 8-hydroxydeoxyguanosine， HIF-1α,ALU-1,LINE-1,Specific Histone Methylations (H3K4 tri- and H3K9 di-methylation) will be measured at 13th, 25th, and 35th week gestation, respectively. To explore: 1) May blood-placenta barrier effectively prevent Ni transfer from maternal blood to fetus or not; 2) May Ni reaching the fetus cause reduction in fetal growth and development or not; 3) May this prenatal exposure to Ni further affect the fetal cardiovascular system or lipid metabolic pathways or not; 4) May Ni taken up by the fetus induce DNA methylation and histone modifications or not; 5) May oxidative stress and inflammatory responses induced by Ni be responsible for such adverse effects of prenatal environmental exposure.