TY - JOUR

T1 - Studying placental transfer of highly purified non-dioxin-like PCBs in two models of the placental barrier

AU - Correia Carreira, S

AU - Cartwright, L

AU - Mathiesen, L

AU - Knudsen, Lisbeth E.

AU - Saunders, Aaron Marc

N1 - Copyright © 2010 Elsevier Ltd. All rights reserved.

PY - 2011/3/1

Y1 - 2011/3/1

N2 - 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 O 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.

AB - 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 O 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.

U2 - 10.1016/j.placenta.2010.12.024

DO - 10.1016/j.placenta.2010.12.024

M3 - Journal article

C2 - 21236486

VL - 32

SP - 283

EP - 291

JO - Placenta

JF - Placenta

SN - 0143-4004

IS - 3

ER -