February 10, 2017
Researchers in the lab of Rebecca Fry, PhD, associate professor of environmental sciences and engineering at the UNC Gillings School of Global Public Health, have explained an underlying biological mechanism by which exposure to cadmium may increase the risk of developing preeclampsia. This potentially life-threatening condition, which can occur during pregnancy, is associated with high blood pressure and high levels of protein in the urine.
The study, led by Fry, who is director of the UNC Superfund Research Program, and first author Samira Brooks, PhD, a postdoctoral fellow working in Fry’s lab, was published in a special December issue of the journal Food and Chemical Toxicology. The issue focused on the role played by microRNAs (miRNAs) – small non-coding RNA molecules that regulate gene expression and control some cellular functions – in toxicology and medicine.
Using a highly translational approach, the researchers integrated analyses of human placental tissue with cell culture experiments to demonstrate that cadmium is correlated with the expression of miRNAs that target the transforming growth factor-beta (TGF-β) pathway. This pathway regulates blood vessel formation and is associated with preeclampsia. Currently, the only treatment option for women with preeclampsia is premature delivery of the placenta, which comes with increased risks for the child. While the cause of preeclampsia is unknown, it has been linked to impaired blood vessels in the placenta, a condition called poor placentation.
Previous research by Fry’s lab has established a significant association between elevated levels of placental cadmium and increased odds of developing preeclampsia (Laine et al., 2015). Other research led by Fry has shed light on potential epigenetic mechanisms in which DNA methylation alterations of the TGF-β pathway correlated with preeclampsia (Martin et al, 2015). The TGF-β pathway, highly involved in controlling vascularization and cell movement, is thought to contribute to the ability of placental cells to migrate and integrate with the mother’s vascular system.
In this study, the researchers wanted to further determine the role cadmium plays in the development of preeclampsia. They hypothesized a role for epigenetic changes, specifically involving dysregulation of miRNAs, which is also a feature of preeclampsia. The researchers compared placental tissue from preeclamptic cases and normotensive controls with varying levels of exposure to cadmium. They also conducted experiments treating placental trophoblast cells to varying concentrations of cadmium. Cadmium levels in both preeclamptic placentas and in placental trophoblast cells were associated with increased expression of genes within the TGF- β pathway, as well as altered expression of miRNAs that target the pathway.
“Only at the interface of clinical and in vitro studies will we begin to truly understand how the environment influences disease to become better equipped for treatment and prevention,” Brooks noted.
“Expectant mothers and women thinking of becoming pregnant need to be aware of potential sources of cadmium — including cigarette smoke, contaminated air from facilities that burn fossil fuels, some foods and even private well water — to better limit their exposure,” said Fry.
Researchers hope this study, and further investigations into the links between the environment, epigenetics and preeclampsia, will lead to development of treatment options for this serious condition.