Environmental Pollutant Polybrominated Diphenyl Ether, a Flame Retardant, Induces Primary Amnion Cell Senescence

Objective Polybrominated diphenyl ethers (PBDEs) are documented to increase the risk for spontaneous preterm birth (PTB). We hypothesize that PBDEs cause oxidative stress (OS) that leads to fetal cell senescence and inflammation associated with PTB. Methods Primary amnion epithelial cells (n = 5) isolated from term, not in labor pregnancies, were exposed to PBDE congeners 47 and 99 (each 5 mu M). ROS kinetics was monitored. Morphologic changes, phospho-p38 MAPK (P-p38) activation, development of senescence, and induction of uterotonins (COX-2 expression) were quantified using light microscopy, Western blot, senescence-associated beta-galactosidase (SA beta-gal) staining, and qRT-PCR, respectively, after 48 and 72 hr of exposure. Results Both PBDE congeners induced ROS within 2 min compared to controls (P < 0.05). P-p38 activation was significant after PBDE-99 treatment than controls (P < 0.05). After 72 hr of treatment, both PBDE-treated cells showed cell death-associated morphologic changes with significantly higher SA beta-gal-stained cells than control. COX-2 expression was higher after 72 hr of treatment with PBDE-99. Overall, the PBDE-99 response was more pronounced than PBDE-47. Conclusions Congener-dependent OS response, p38 MAPK activation, senescence, and COX-2 expression were seen in human amnion cells by PBDEs. These findings demonstrate environment pollutant-induced senescence activation and inflammation can lead to pathways resulting in PTB.