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Environmental Factor, November 2015

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Placental cadmium linked to increased risk of preeclampsia

By Sara Mishamandani and Carol Kelly

Rebecca Fry

Fry’s lab studies how environmental exposures are associated with human disease, with a particular focus on genomic and epigenomic factors. (Photo courtesy of Rebecca Fry)

Cadmium levels in the placenta during pregnancy are associated with the risk of developing preeclampsia, according to a recent NIEHS-funded study from the University of North Carolina at Chapel Hill (UNC) Superfund Research Program (SRP) Center.

Preeclampsia during pregnancy is associated with high blood pressure and high levels of protein in the urine. It may contribute to the development of later-life cardiovascular disease and chronic kidney disease in the child. If untreated, it can also lead to an onset of seizures that pose a serious threat to the mother and baby.

The researchers, led by metals toxicologist Rebecca Fry, Ph.D., an associate professor at the UNC Gillings School of Global Public Health, also looked at the interactions between the mother’s level of cadmium, a toxic metal, and the essential metals selenium and zinc. They found that selenium and zinc may play a role in protecting against cadmium-associated preeclampsia.

This study, published in the journal PLOS ONE, is the first to address the interactions among cadmium, essential metals in the placenta, and the odds of developing preeclampsia in pregnant women. People can be exposed to cadmium from cigarette smoke, contaminated air from facilities that burn fossil fuels, and some foods.

Measuring metals in the placenta

Researchers selected 172 subjects with and without preeclampsia for a case-control study from the larger Maternal Oral Therapy to Reduce Obstetric Risk (MOTOR) study at UNC, which recruited pregnant women from the southeastern United States. Researchers used sensitive trace metals analysis to measure levels of cadmium, selenium, and zinc in placental tissue obtained after delivery. The range of concentrations of cadmium in the study was consistent with levels generally found in the U.S. and globally.

The scientists found that placental cadmium levels were significantly associated with preeclampsia. This relationship changed when they analyzed it in the context of selenium and zinc levels. Lower levels of zinc and selenium increased the odds for preeclampsia compared with the odds based on high cadmium levels alone. According to the authors, the findings suggest that zinc and selenium may play a role in protecting pregnant women from cadmium-associated preeclampsia.

“These data support a critical public health issue — namely, that prenatal exposure to toxic metals has the potential to harm pregnancies,” said Fry. “The data also suggest that studying the interaction between these metals may be more biologically relevant than studying single metals alone. Our next steps are to understand the biological mechanisms that underlie the identified risk associations in humans, using systems toxicology and cell culture-based tools.”

Epigenetics and preeclampsia

The precise trigger for preeclampsia is unknown, but it has been linked to impaired blood vessels in the placenta, a condition known as poor placentation. In a step toward understanding its cause, Fry led a study to identify epigenetic changes associated with the disease.

Her lab discovered that a decrease in CpG methylation, a type of epigenetic change that can change how DNA is expressed, altered the action of genes in the pathway that produces transforming growth factor-beta, a substance that controls cellular function. This alteration in genetic programming may be a major contributor to preeclampsia.

Citations: Laine JE, Ray P, Bodnar W, Cable PH, Boggess K, Offenbacher S, Fry RC. 2015. Placental cadmium levels are associated with increased preeclampsia risk. PLOS One 10(9): e0139341.

Martin E, Ray PD, Smeester L, Grace MR, Boggess K, Fry RC. 2015. Epigenetics and preeclampsia: defining functional epimutations in the preeclamptic placenta related to the TGF-β pathway. PLoS One 10(10):e0141294.

(Sara Mishamandani is a research and communication specialist and Carol Kelly is a science writer for MDB Inc., a contractor for the NIEHS Division of Extramural Research and Training.)

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