Abstract
Perfluorooctane sulfonate (PFOS), a synthetic chemical used in various commercial applications and industrial settings, has led to contamination of drinking water and has been detected in the bloodstream of pregnant women with gestational complications. Recent investigations have indicated that PFOS disrupts placental function; however, the mechanism remains elusive. Given the significant abundance of mitochondria in the placenta, which play a pivotal role in fulfilling the heightened energy requirements of pregnancy, our research aimed to examine the repercussions of PFOS exposure on mitochondrial dynamics within placental trophoblasts. Specifically, human trophoblasts (HTR-8/SVneo) were exposed to environmentally relevant concentrations of PFOS ranging from 0.1 to 50 μM for 48 hours. Findings revealed that PFOS exposure elicited a concentration-dependent decrease in basal, maximal, and ATP-linked respiration. PFOS inhibited the activity of electron transport complexes I, II, and III, resulting in diminished ATP production. Furthermore, PFOS reduced mitochondrial DNA copy number, indicating less mitochondrial content. Concurrently, there was a downregulation in the expression of mitochondrial biogenesis-related genes, including PGC-1α, NRF1, and NRF2. Notably, PFOS perturbed mitochondrial dynamics by suppressing the expression of fission-related genes (FIS1 and DRP1) and fusion-related genes (MFN1 and MFN2). In summary, our findings suggest that PFOS exposure leads to a decline in mitochondrial content and compromises the bioenergetic capacity of trophoblasts by impairing cellular respiration. This reduction in mitochondrial biogenesis and alterations in fission/fusion dynamics induced by PFOS may contribute to mitochondrial dysfunction in trophoblasts. Consequently, strategies that preserve mitochondrial function in trophoblasts may mitigate PFOS-induced impairment of placental energy metabolism.