Preterm birth is a leading cause of infant mortality that can lead to poor life-long health and adverse neurodevelopmental outcomes. The physiologic mechanisms that precede preterm labor remain elusive, and the role that epigenetic phenomena play is largely unstudied with recent data showing that increased levels of microRNA (miRNA) were directly related to shortened gestational periods. Now, a study from researchers at the Mount Sinai Health System and Harvard Medical School has established a link between mercury and lead exposure and cervical miRNA expression. The team state that their study shows the influence miRNAs have on gestational age at the time of delivery, and environmental contaminants that factor into miRNA expression.
Previous studies show that microRNA expression is tissue-specific, however, a single miRNA can regulate the expression of hundreds of target genes downstream. They play a critical role in embryonic development, the body’s inflammatory response, and signaling pathways that are vital to labor and delivery. Earlier studies from the lab identified six miRNAs that had higher expression in pregnancies with shorter gestations, an important step in increasing the ability to predict and prevent preterm labor. The current study investigates miRNA expression, seeking to understand environmental factors that prompt miRNA to express abnormally in the cervix.
The current study used cervical swabs from 60 pregnant women and quantified cervical miRNA expression; the women’s blood lead, bone lead and toenail mercury levels were also analyzed. Results show that seventeen miRNAs were negatively associated with toenail mercury levels, and tibial bone lead levels were associated with decreased expression of miR-575 and miR-4286. Data findings identify miRNAs in the human cervix as novel responders to maternal chemical exposure during pregnancy.
The group explain that they focused on lead and mercury exposure as possible causes, as metals are common environmental contaminants. They go on to add that studying their relation to epigenetic changes helps clarify the role of environmental factors in gestation and preterm birth. The researchers conclude that, to their knowledge, this is the first study to evaluate the effects of metals on cervical miRNA, suggesting a possible environmentally mediated mechanism of miRNA gene regulation during pregnancy.
The team surmise that their work provides insight into the influences epigenetic factors like miRNA have on preterm birth and which environmental factors underpin this miRNA expression. For the future, the researchers state that improvements in preterm birth prediction promise to have a major impact on patient care. They go on to add that new biomarkers with improved prediction ability could help to better target therapies for pregnancies at risk for preterm delivery and novel interventions could be designed to interrupt the cascade of molecular events that occur to trigger labor and produce preterm birth.
Source: The Mount Sinai Health System