Modeling placental transport: correlation of in vitro BeWo cell permeability and ex vivo human placental perfusion

TY - JOUR

T1 - Modeling placental transport: correlation of in vitro BeWo cell permeability and ex vivo human placental perfusion

AU - Poulsen, Marie Sønnegaard

AU - Rytting, Erik

AU - Mose, Tina

AU - Knudsen, Lisbeth E

N1 - Keywords: Antipyrine; Benzoic Acid; Caffeine; Cell Line; Cell Membrane Permeability; Female; Glycine; Humans; Kinetics; Maternal Exposure; Maternal-Fetal Exchange; Models, Biological; Perfusion; Placenta; Pregnancy

PY - 2009

Y1 - 2009

N2 - The placental passage of three compounds with different physicochemical properties was recently investigated in ex vivo human placental perfusion experiments (caffeine, benzoic acid, and glyphosate) [Mose, T., Kjaerstad, M.B., Mathiesen, L., Nielsen, J.B., Edelfors, S., Knudsen, L.E., 2008. Placental passage of benzoic acid, caffeine, and glyphosate in an ex vivo human perfusion system. J. Toxicol. Environ. Health, Part A 71, 984-991]. In this work, the transport of these same three compounds, plus the reference compound antipyrine, was investigated using BeWo (b30) cell monolayers. Transport across the BeWo cells was observed in the rank order of caffeine>antipyrine>benzoic acid>glyphosate in terms of both the apparent permeability coefficient and the initial slope, defined as the linear rate of substance transferred to the fetal compartment as percent per time, a parameter used to compare the two experimental models. The results from the in vitro studies were in excellent agreement with the ex vivo results (caffeine approximately antipyrine>benzoic acid>glyphosate). However the transfer rate was much slower in the BeWo cells compared to the perfusion system. The advantages and limitations of each model are discussed in order to assist in the preparation, prediction, and performance of future studies of maternal-fetal transfer.

AB - The placental passage of three compounds with different physicochemical properties was recently investigated in ex vivo human placental perfusion experiments (caffeine, benzoic acid, and glyphosate) [Mose, T., Kjaerstad, M.B., Mathiesen, L., Nielsen, J.B., Edelfors, S., Knudsen, L.E., 2008. Placental passage of benzoic acid, caffeine, and glyphosate in an ex vivo human perfusion system. J. Toxicol. Environ. Health, Part A 71, 984-991]. In this work, the transport of these same three compounds, plus the reference compound antipyrine, was investigated using BeWo (b30) cell monolayers. Transport across the BeWo cells was observed in the rank order of caffeine>antipyrine>benzoic acid>glyphosate in terms of both the apparent permeability coefficient and the initial slope, defined as the linear rate of substance transferred to the fetal compartment as percent per time, a parameter used to compare the two experimental models. The results from the in vitro studies were in excellent agreement with the ex vivo results (caffeine approximately antipyrine>benzoic acid>glyphosate). However the transfer rate was much slower in the BeWo cells compared to the perfusion system. The advantages and limitations of each model are discussed in order to assist in the preparation, prediction, and performance of future studies of maternal-fetal transfer.

U2 - 10.1016/j.tiv.2009.07.028

DO - 10.1016/j.tiv.2009.07.028

M3 - Journal article

C2 - 19647068

SN - 0887-2333

VL - 23

SP - 1380

EP - 1386

JO - Toxicology in Vitro

JF - Toxicology in Vitro

IS - 7

ER -