PFBS disrupts lipid metabolism and mitochondrial function in human trophoblast cells.

Perfluorobutanesulfonic acid (PFBS) is an emerging short-chain per- and polyfluoroalkyl substance (PFAS), a group of persistent environmental contaminants associated with adverse reproductive outcomes. The placenta plays a critical role in the pathogenesis of pregnancy complications, and disrupted placentation is implicated in the mechanistic pathways linking PFBS exposure to these disorders. In particular, placental mitochondria function refines during pregnancy to optimize the dynamic growth of the fetus and placenta. Disruptions in mitochondrial function may therefore mediate the adverse effects of environmental exposure on pregnancy outcomes. This study investigated the effects of PFBS on the metabolism and mitochondrial function of human syncytiotrophoblast (STB), the primary nutrient-transporting cells of the placenta. Using a human trophoblast stem cell model, we differentiated cells into STBs and exposed them to an environmentally relevant dose of PFBS (100 µM) for 24 h. Transcriptomic (RNA-seq) analysis identified 22 downregulated genes and 10 upregulated genes (FDR < 0.05). Integrated transcriptomic and metabolomic analyses revealed that PFBS significantly disrupted lipid metabolism, notably downregulating PPARG, a key regulator of placental lipid homeostasis, and carnitine shuttle genes CPT1A and SLC25A20, which are essential for mitochondrial fatty acid import. Further functional assessments found increased mitochondrial DNA copy number, yet decreased ATP production, indicating mitochondrial dysfunction. However, PFBS exposure did not induce oxidative stress nor alter mitochondrial morphology. These findings demonstrate that PFBS induces metabolic toxicity in human STBs, primarily by disrupting lipid metabolism and mitochondrial energy production. This mechanism may underlie the observed associations between PFBS exposure, placental dysfunction, and adverse pregnancy outcomes.

Duke Scholars

Author Liping Feng Obstetrics and Gynecology, Reproductive Sciences