胚胎宫内生长受限（IUGR）是指在子宫内生长缓慢。IUGR会进一步导致新生儿后天发育迟缓等异常。妊娠期大气污染物暴露是IUGR的重要诱因。同时，妊娠期妇女的PM2.5的暴露损伤，也是我国公众关心的问题。目前PM2.5暴露导致IUGR的研究多是在西方进行的。我国典型地区大气PM2.5对妊娠期体内胎儿的影响程度及诱发IUGR的风险，存在诸多研究空白。本项目旨在检测如下假设：我国PM2.5和主要组分，具有妊娠期暴露导致IUGR的毒理作用，且胎盘为主要介导器官。 为此，(一)我们建立动物模型，开展妊娠期PM2.5暴露试验，试验条件包括: 洁净空气，自然大气，以及PM2.5主要组分。(二)测量妊娠期PM2.5后幼鼠发育表型：孕期长度，出生体重等。 (三)胎盘组织的生物分子组学，利用系统生物组学方法，阐明妊娠期PM2.5暴露影响胎盘发育和功能，进而导致IUGR的细胞和分子毒理机制。

Intrauterine growth restriction (IUGR) refers to poor growth of a fetus while in the mother's womb during pregnancy. The causes can be many, and include exposure to ambient air pollutant. IUGR is linked to postnatal development abnormality and disease risks. Fine particles (e.g., PM2.5) are important components in air pollution in China, and attracted increasing concerns regarding to their adverse impact on human health. Pregnant women and fetus in uterus are particular susceptible to toxic pollutants; however, the impact of PM2.5 in China and its chemical components on IUGR risk is poorly studied. This proposal is consist of three inter-connected aims. (1) We take advantage of the established systems in investigators’ labs at Tongji University to synthesize the primary components of PM2.5 in China. The concentration, diameter and chemical composition of the PM2.5 is precisely controlled in the lab. Pregnant mice will be exposure to the synthesized PM2.5 in specially designed chambers, where the exposure conditions are closely monitored in real-time. Four PM2.5 components along with Shanghai ambient air and filtered clean air will be given to identical groups of mice. We will also investigate the susceptibility to PM2.5 during early stage of pregnancy and middle stage of pregnancy, which are critical periods of blastocyst formation, implantation and organogenesis. (2) Phenotype will be measured at birth (birth count, birth weight, placenta weight and gestational age). Placenta is the key organ controlling the access of oxygen and nutrition to the fetus, as well as toxic chemicals. Placenta tissue will be collected from each exposure group, and profiled for whole transcriptome and DNA methylation. (3) We will conduct systems biology analysis aiming to understand the molecular mechanisms (gene, pathway, co-expression networks, etc) that PM2.5 exposure alternate placenta function and result in IUGR. The analysis also identifies biomarker in placenta which indicate the damage due to PM2.5 exposure during pregnancy.