During an NIEHS lecture on October 6, Ilana Elkin, Ph.D.An assistant professor of environmental health at San Diego State University, San Diego State University, described how a chemical called trichlorethylene (TCE) can interfere with a fetus’s development in the womb.

Ilana Elkin, Ph.D. Elkin is an assistant professor of environmental health at San Diego State University, where she works with a long-term goal of understanding the role that environmental chemicals play in adverse birth outcomes. (Photo courtesy of Ilana Elkin)

TCE has been widely used in the past in the manufacture of coolants and metal degreasing agents. Despite government efforts to clean up TCEs and prevent further pollution, inherited soil and water pollution persists.

“TCE is a widespread environmental pollutant that has been detected in more than half Superfund sites“Pregnant women may be exposed to TCE by drinking contaminated water,” explained Elkin, a former NIEHS Superior Research Program (SRP) intern and 2019 Karen Wetterhahn Award recipient.

After TCE is consumed, the chemical can enter the bloodstream and cross into the placenta, an important organ during pregnancy that provides oxygen and nutrients to the developing fetus and breaks down the toxic substances it encounters. According to Elkin, these factors make the placenta more susceptible to toxicity.

“Through my research, I wanted to understand how exposure to TCE can harm the placenta at the molecular level,” Elkin said.

Gender differences

Previous studies have shown associations between exposure to TCE and low birth weight, among other adverse birth outcomes. Elkin’s research seeks to uncover the underlying mechanism.

“In most cases, we don’t know what causes negative birth outcomes, beyond factors like genes, infection, or behaviors like smoking and drinking alcohol,” Elkin said. “My job as an environmental toxicologist is to study the role that pollutants play in causing these devastating effects that can have short- and long-term health consequences for mothers and children.”

Elkin explains her laboratory group’s study of mice links exposure to TCE before birth 10% less birth weight. They discovered that the effect was more pronounced in male offspring than in female offspring.

Because males and females differ at the molecular level in their DNA and hormone synthesis, Elkin investigated how TCE affects gene expression in the placenta. Gene expression is the process by which the information encoded in DNA is used to make proteins.

have found Greater differences in gene expression In the placentas of female offspring of male offspring after exposure to TCE, compared to unexposed offspring. Specifically, it detected increased expression of genes responsible for responding to stress, and decreased expression of genes involved in the assembly and transport of mitochondria, the part of the cell that produces energy.

“While females showed more differences in gene expression than males, males were more likely to have low birth weight,” Elkin said. “These differences may be because the genes expressed by females were largely an adaptive response to defend against exposure to toxicants.”

Karen Weathercock Karen Weatherhan, whose namesake for the Weatherhan Memorial Prize, has promoted interdisciplinary science, counseling, and community education throughout her career. Elkin gave the Veterhan Memorial Lecture in her honor. (Photo courtesy of Dartmouth College Library)

Toxicity in human placental cells

Elkin shared that in the human body, TCE can be metabolized to form S-(1,2-dichlorovinyl)-L-cysteine, or DCVC, a highly reactive compound with the potential to damage cells.

She suspected that DCVC might be responsible for effects in the placenta that lead to low birth weight, so she conducted additional trials with human placental cells. It again looked at gene expression and analyzed the cells’ rates of oxygen consumption, which measures the ability of mitochondria to produce energy.

“In the shorter exposure periods, the cells initially increased their rate of oxygen consumption as a result of the stress,” Elkin said. “However, after prolonged exposure, oxygen consumption decreased as cells lost the ability to adapt to stressors, making them more susceptible to cell death.”

According to Elkin, results from both the rat study and the cell study suggest that TCE may lead to mitochondrial dysfunction and a high stress response in the placenta, which may contribute to an increased risk of adverse birth outcomes.

Toxic substances and pathogens

Elkin plans to further research how exposure to pollutants disrupts placental processes during pregnancy.

“I also hope to research how toxins and pathogens interact during pregnancy,” Elkin said. “During this era of COVID-19, it is increasingly important to understand how mixtures of exposure affect the health of mothers and children.”

As Elkin’s career developed, she continued to demonstrate Witterhan’s dedication to science and mentorship.

“The Wetterhahn Award is a recognition of outstanding SRP investigators,” said William Sock, Director of SRP. “Ilana is more than just a good researcher – she gives back to the community, understands interdisciplinary research, and acts as a mentor to other students.”

quotes:
Owner AL, Harris SM, Elkin ER, Karnovsky A, Colacino JA, Loch-Caruso R. 2022. Trichlorethylene modifies energy metabolites in the amniotic fluid of Wistar rats. Reprod Toxicol 109: 80-92.

Elkin AR, Bakulsky km, Colacino GA, Bridges D, Kilburn PA, Armant DR, Loch Caruso AR. 2021. Transcriptional profiling of the response to the metabolite trichlorethylene S-(1,2-dichlorovinyl)-L-cysteine ​​revealed activation of the eIF2α/ATF4 integrated stress response in two in vitro placental models. Arch Toxicol 95 (5): 1595-1619.

Elkin AR, SO AL, Kilburn PA, Bakulsky KM, Armant DR, Loch Caruso AR. 2022. Toxicity assessments of selected metabolites of trichloroethylene and perchloroethylene in three in vitro human placental models. Reprod Toxicol 109: 109-120.

(Lauren Sprouse is a science communications specialist at MDB, Inc., and is a contractor with the NIEHS Superfund Research Program.)

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