Dr. Rebecca Fry, a professor at the University of North Carolina at Chapel Hill, was awarded the 2021 SOT Translational Impact Award for her translational research on developmental toxicants and public health. Her Award Lecture during the 2021 SOT Annual Meeting and ToxExpo, “The Placenta: A Recorder and Transducer of Environmental Toxics,” described how her research has utilized different models, such as cells, mice, and human cohorts, to study the interplay between environmental toxicants, the placenta, and children’s health.
The placenta is well known for being responsible for nutrient transfer and waste exchange between mother and fetus during pregnancy. What is less known is that although the placenta is temporary, it can have long-lasting health implications. Dysfunction in the placenta can lead to diseases of pregnancy and diseases later in life. The placenta also is an intermediary for environmental toxicants, and placental research can give important insights into the effects of xenobiotics on maternal and fetal health.
Dr. Fry opened her Award Lecture by describing the effects of inorganic arsenic during pregnancy. Early life exposure to arsenic has been associated with later-life health outcomes both in mice and in humans. In areas of Bangladesh where the water is highly contaminated with arsenic, babies showed extensive gene changes following in utero exposure to arsenic. Similar results were seen in a human study in North Carolina in areas where inorganic arsenic was found in private drinking water wells.
In another cohort in Mexico, Dr. Fry and her team saw that prenatal arsenic exposure was associated with lower birthweight. Further exploring the mechanisms that underlie this, Dr. Fry showed that cord blood leukocytes from these pregnancies had DNA methylation in imprinted genes that could link prenatal arsenic exposure to lower birthweight. Experiments with placental cells bolstered this hypothesis; exposing cells to inorganic arsenic led to glucocorticoid receptor pathway disruption via DNA methylation.
Cadmium is another toxic metal associated with reproductive health. According to Dr. Fry, increased cadmium in the placenta increases the risk of preeclampsia, a dangerous condition of high blood pressure in pregnant women. Preeclampsia is a leading cause of poor fetal outcomes across the world and is hypothesized to involve placental cells failing to migrate where they should during pregnancy.
Women with preeclampsia have been found to have disruptions in the transforming growth factor (TGF)-beta pathway in their blood and placenta. This is hypothesized to occur because TGF-beta decreases the normal invasion and migration of placental cells, leading to increased preeclampsia risk. Using cell culture, Dr. Fry and her lab showed that the negative effects of cadmium on cell migration could be minimized by turning off the TGF-beta pathway with inhibitors, allowing normal placental cell migration to proceed. Epigenetic regulation of the TGF-beta pathway by using microRNAs had a similar effect on placental cell migration in their experiments.
Dr. Fry’s last contaminant example was the class of chemicals called per- and poly-fluoroalkyl substances, or PFAS. PFAS accumulate in the placenta and can disrupt placental cells, and PFAS exposure during pregnancy is associated with decreased fertility and increased risk of preeclampsia. As part of her research with the PFAS Testing Network in North Carolina, Dr. Fry used a translational approach to explore the relationship between human PFAS exposure during pregnancy and placental function in a high-risk pregnancy cohort. Several PFAS were detected in their placental samples. Placental cells also were used to look at the mechanisms of PFAS toxicity. Some specific PFAS, such as perfluorooctane-sulfonate (PFOS), perfluorooctanoic acid (PFOA), and GenX, decreased the migration of placental cells—potentially providing a mechanistic link between PFAS exposure and increased preeclampsia.
Plenty of great placenta research is ongoing among SOT members (for more, check out another session from this year’s Annual Meeting on the placenta and environmental exposure). Dr. Fry’s research highlights exactly why this placenta research is so important. Dr. Fry’s Award Lecture was a fantastic example of applying and expanding toxicology research to improve public health and lead to healthier pregnancies. Her translational research demonstrates how vital the placenta is for studying environmental exposures, especially during pregnancy.
This blog was prepared by an SOT Reporter and represents the views of the author. SOT Reporters are SOT members who volunteer to write about sessions and events in which they participate during the SOT Annual Meeting and ToxExpo. SOT does not propose or endorse any position by posting this article. If you are interested in participating in the SOT Reporter program in the future, please email Giuliana Macaluso.
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