title: Studying placental transfer of highly purified non-dioxin-like PCBs in two models of the placental barrier.
abstract: Currently, toxicology and toxicokinetics of purified non-dioxin-like polychlorinated biphenyls (NDL-PCBs) are poorly characterised. Transplacental kinetics of NDL-PCBs can be studied in a variety of models, but careful validation of each model is crucial. We aimed to develop a standard operating procedure for establishing an in vitro model of the human placental barrier. Using this model, we sought to investigate placental transport kinetics of two NDL-PCB congeners. Firstly, we compared the BeWo cell line of the American Type Culture Collection with the BeWo b30 clone and determined parameters for monolayer formation. Secondly, we performed placental perfusions to validate the in vitro model. To that end, the transport of radiolabelled PCB52 and 180 was investigated in both models. We were not able to grow the ATCC cell line to confluency, but determined monolayer formation using BeWo b30. A confluent monolayer is present by day 4 post-seeding, transepithelial electrical resistance being 44.65 ± 11.06 Ω cm(2) and sodium fluorescein transport being 4.1% ± 0.18. Both measures can be used as indicators for monolayer formation. Results from kinetic studies in vitro and ex vivo were in excellent agreement. Both NDL-PCBs crossed the placental barrier within 2.5 h. We found PCB180 to transfer more rapidly and PCB52 to associate more with placental tissue. Since transport and association patterns were similar in vitro and ex vivo, we conclude that the protocol provided here forms the basis for a good model of the placental barrier using BeWo b30. We hypothesise that the observed differences in transport and association patterns of NDL-PCBs may indicate that toxic effects of PCB52 play a more important role regarding placental function, whereas PCB180 may be of greater importance for fetal toxicity.
authors.affiliation: Bristol Initiative for Research of Child Health, Biophysics Research Unit, University Hospitals Bristol NHS Foundation Trust, St. Michael's Hospital, Southwell Street, BS2 8EG Bristol, UK. s.carreira@bristol.ac.uk
authors.forename: S
authors.initials: S
authors.lastname: Correia Carreira
authors.forename: L
authors.initials: L
authors.lastname: Cartwright
authors.forename: L
authors.initials: L
authors.lastname: Mathiesen
authors.forename: L E
authors.initials: LE
authors.lastname: Knudsen
authors.forename: M
authors.initials: M
authors.lastname: Saunders
mesh_terms: D045744:Cell Line, Tumor; D005260:Female; D005333:Fetus; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D010920:Placenta / Q000378:metabolism*; D011078:Polychlorinated Biphenyls / Q000032:analysis / Q000493:pharmacokinetics* / Q000633:toxicity; D011247:Pregnancy
chemical_list: C009407:2,5,2',5'-tetrachlorobiphenyl; C410127:PCB 180; D011078:Polychlorinated Biphenyls