Environmental Pollutants and Placental Transcriptome

Transport proteins in trophoblast cells/placenta protect fetus from maternal toxins by taking part in transplacental displacement of the xenobiotics (transfer to, removal from the cells). Environmental pollutants; might interact with transport proteins, increase and decrease their expression, cause functional disorders with toxicokinetic and toxicodynamic interactions. As main protective component of barrier is disrupted, fetus is more prone to undesirable effects such as congenital neoplasia, growth retardation, preterm delivery, vitamin D deficiency, systemic inflammation, low birth weight, preterm delivery, gestational hypertension, preeclampsia, changes in epigenetics and glucose metabolism which create a basis of adult coronary artery and diabetes, and even abortus in fetal death. Among environmental pollutants; persistent organic pollutants (POPs) are considered of global concern, due to transport to long distances persistance in environment, bioaccumulation and biomagnification in the ecosystem. Differences between species and strains exist regarding the expression and function of transport proteins; as level and expression of expression and metabolism could be different. However, environmental factors play a common role between species in etiology and pathogenesis of diseases. Majority of the researches focused on determination of concentration of the pollutants, effects of pollutants on the fetus, expression of a limited number of placental membrane proteins. From point of realistic exposure scenarios (mixture/low-dose exposure) limited studies are available. Therefore, the aim of study is to investigate relationship between environmental pollutants and placental transport proteins. In the first stage of the project; human and dog placenta will be evaluated for 28 pollutants using GC-MS (PCB, PBDE, PAH, Organochlorine pesticides) and gene expression of placental membrane transport proteins using microarray. Correlation between GC-MS and microarray results and in-silico analysis would provide vast information on contaminant and transport protein relation. The second phase of project is experimental-analytical designed unlike the first phase, which is cross-sectional and descriptive. Thus, the results of study will reveal function of transplacental proteins in determining maternal-fetal barrier activity for healthy fetal development. Due to in-utero exposure, as it is not capable for removal of these xenobiotics effectively and the organ system, with lower amount and function of detoxification enzymes and other clearance mechanisms, fetus is the most sensitive group to environmental pollutants among the population. Therefore, exploration of transport proteins and other mechanisms, will form basis for advanced pharmacological researches in establishing and supporting mechanisms to prevent the transmission of environmental pollutants to fetus.