Hofmann Alissa, Mishra Jay S, Yadav Pankaj, Dangudubiyyam Sri Vidya, Blesson Chellakkan S, Kumar Sathish
Endocrinology-Reproductive Physiology Program, University of Wisconsin, Madison, WI 53715, USA.
Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706, USA.
J Environ Sci Public Health. 2023;7(4):164-175. Epub 2023 Oct 10.
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 and . Notably, PFOS perturbed mitochondrial dynamics by suppressing the expression of fission-related genes ( and ) and fusion-related genes ( and ). 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.
全氟辛烷磺酸（PFOS）是一种用于各种商业应用和工业环境的合成化学品，已导致饮用水污染，并在患有妊娠并发症的孕妇血液中被检测到。最近的调查表明，PFOS会破坏胎盘功能；然而，其机制仍不清楚。鉴于胎盘中线粒体数量众多，而线粒体在满足妊娠期间增加的能量需求方面起着关键作用，我们的研究旨在检查PFOS暴露对胎盘滋养层细胞中线粒体动力学的影响。具体而言，将人滋养层细胞（HTR-8/SVneo）暴露于浓度范围为0.1至50μM的与环境相关的PFOS中48小时。研究结果显示，PFOS暴露导致基础呼吸、最大呼吸和ATP偶联呼吸呈浓度依赖性下降。PFOS抑制了电子传递复合物I、II和III的活性，导致ATP生成减少。此外，PFOS降低了线粒体DNA拷贝数，表明线粒体含量减少。同时，线粒体生物发生相关基因（包括 和 ）的表达下调。值得注意的是，PFOS通过抑制与裂变相关的基因（ 和 ）和与融合相关的基因（ 和 ）的表达来扰乱线粒体动力学。总之，我们的研究结果表明，PFOS暴露会导致线粒体含量下降，并通过损害细胞呼吸来损害滋养层细胞的生物能量能力。PFOS诱导的线粒体生物发生减少以及裂变/融合动力学改变可能导致滋养层细胞线粒体功能障碍。因此，保护滋养层细胞线粒体功能的策略可能会减轻PFOS诱导的胎盘能量代谢损伤。
