DNTP study shows how PFAS might harm the placenta
Per- and polyfluoroalkyl substances (PFAS) may directly target the placenta, disrupting cellular function and the activity of genes that are critical for proper development, well below toxic levels, according to researchers from the NIEHS Division of the National Toxicology Program (DNTP).
PFAS are ubiquitous environmental contaminants that have been associated with pregnancy complications involving the placenta, which delivers oxygen and nutrients to the fetus. Adverse developmental and reproductive outcomes have been investigated for relatively few PFAS, and the underlying mechanisms remain unclear. There is an immense knowledge gap regarding the placental toxicity of the more than 600 PFAS compounds currently in United States commerce.
Using a high-throughput toxicity screen (HTTS), the researchers evaluated the effects of 42 PFAS on human placental cells called trophoblasts. According to the authors, this work describes the first PFAS HTTS using a placental cell line. Several compounds of high public health interest severely inhibited trophoblast migration, which is important for embryonic implantation, fetal growth, and the prevention of certain pregnancy complications.
Two of these compounds — perfluorooctanoic acid (PFOA) and ammonium perfluoro-2-methyl-3-oxahexanoate (GenX) — altered the activity of genes that are vital to placental health and cellular responses to stress at treatment levels 5- to 150-fold lower than those causing cytotoxicity. Taken together, the results highlight the potential of these compounds to disrupt critical aspects of trophoblast biology, such as proliferation, migration, and mitochondrial function.
Citation: Blake BE, Rickard BP, Fenton SE. 2022. A high-throughput toxicity screen of 42 per- and polyfluoroalkyl substances (PFAS) and functional assessment of migration and gene expression in human placental trophoblast cells. Front Toxicol 4:881347.