Researchers have long associated per- and polyfluoroalkyl substances (PFAS), commonly known as “forever chemicals,” to certain severe birth defects, but exactly how these pollutants harm a developing fetus has remained mostly a mystery. New research now provides the first clear molecular explanation, showing how one PFAS, called perfluorodecanoic acid (PFDA), can trigger craniofacial abnormalities before birth.

The research was published today in ACS Chemical Research in Toxicology.

There are approximately 15,000 PFAS used in consumer and industrial products but scientists are increasingly finding that only some pose serious health risks. In this study, Lampe worked with the paper’s first author Michaela Hvizdak and co-author Sylvie Kandel to test 13 commonly found PFAS and discovered PFDA as the most toxic during fetal craniofacial development.

They demonstrated a possible link between PFDA and the extensive facial changes observed in humans and laboratory animals, with some estimates indicating a 10% increased risk at extremely low exposure levels. 

“This finding moves us beyond association by providing a clear explanation for how PFDA can interfere with fetal development. It’s a critical step toward understanding a vast and complex class of environmental chemicals,” said Dr. Jed Lampe.

They found that PFAS disrupts retinoic acid, a molecule essential for shaping the face and head during early pregnancy. Retinoic acid regulates hundreds of genes and its levels must be controlled. Because a fetus cannot produce or safely eliminate excess retinoic acid, it relies entirely on the mother to maintain the homeostatic balance of the hormone.

Funded by a two-year, nearly $350,000 grant from the National Institutes of Health’s National Institute on Aging, the University of Cincinnati’s Shawn Xiong, PhD, is analyzing real-world patient data to learn more about how GLP-1 drugs affect people with mild cognitive impairment, a common precursor to Alzheimer’s disease.

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