Air pollution and placental mitochondrial DNA copy number: Mechanistic insights and epidemiological challenges

During embryogenesis and embryo implantation, the copy number of mtDNA is elaborately regulated to meet the cellular demand for division, growth and differentiation. With large numbers of mitochondria for energy production, placental cells possess strong endocrine functionalities and capacities for efficient signaling communication. Recently, several environmental epidemiological studies have shown an association between mitochondrial DNA copy number, adverse birth outcomes and maternal exposure to air pollution, which has shed light on the possible effect of pollutants on placental molecular events. Because the mtDNA replication is thought to be a direct drive of mtDNA change, we tried to highlight the essential factors involved in the process of mtDNA replication. Then we traced the mtDNA change in the formation of placenta during embryogenesis, and evaluated the importance of mitochondrial genome maintenance during gestation. The possible mechanism from the epidemiological and experimental studies were reviewed and summarized, and recommendations were proposed for future studies to improve the precision of the estimated difference. The issue will be well-understood if the integrated profiles, such as familial genetic tendency, maternal genetic information, identification of mitochondrial DNA copy number in each placental cell type, and total personal exposure assessment, are considered in the future study.