Transport of Benzo[α]pyrene in the Dually Perfused Human Placenta Perfusion Model: Effect of Albumin in the Perfusion Medium

Abstract

Transport of benzo [a]pyrene (BaP) across the placenta was examined because it is a ubiquitous and highly carcinogenic substance found in tobacco smoke, polluted air and certain foods. Foetal exposure to this substance is highly relevant but is difficult to estimate. The human placenta is unique compared to other species; since it is available without major ethical obstacles, we have used the human placenta perfusion model to study transport from mother to foetus. Placentas were donated after births at Rigshospitalet in Copenhagen from pregnant mothers who signed an informed consent. BaP is lipophilic and studies using cell culture medium in 6-hr placenta perfusions showed minimal transport through the placenta. To increase the solubility of BaP in perfusion medium and to increase physiological relevance, perfusions were also performed with albumin added to the perfusion medium [2 and 30 mg/ml bovine serum albumin (BSA) and 30 mg/ml human serum albumin (HSA)]. The addition of albumin resulted in increased transfer of BaP from maternal to foetal reservoirs. The transfer was even higher in the presence of an HSA formulation containing acetyltryptophanate and caprylate, resulting in a foetal-maternal concentration (FM) ratio of 0.71 € 0.10 after 3 hr and 0.78 € 0.11 after 6 hr, whereas the FM ratio in perfusions without albumin was only 0.05 € 0.03 after 6 hr of perfusion. Less BaP accumulated in placental tissue in perfusions with added albumin. This shows that transplacental transport of the pro-carcinogenic substance BaP occurs, and emphasizes the importance of adding physiological concentrations of albumin when studying the transport of lipophilic substances.

Vessel tortuousity and reduced vascularization in the fetoplacental arterial tree after maternal exposure to polycyclic aromatic hydrocarbons

“…In addition, PAHs may act directly on the embryo to negatively affect its growth. Certainly PAHs are able to cross the perfused human placenta in vitro (30), and high doses given to pregnant rats cause fetal vascular hemorrhage (49). These results suggest that PAH exposure can have direct fetal effects.…”

Determination of the Transport Rate of Xenobiotics and Nanomaterials Across the Placenta using the <em>ex vivo</em> Human Placental Perfusion Model

“…It lacks blood flow and the integrity of the monolayer has to be evaluated carefully since it depends on several factors like cell culture conditions, seeding density, exposure duration and the membrane insert 6,29 . Different xenobiotics and also nanoparticles bind to various plasma proteins which can significantly influence the transplacental transfer 31 ; considering the binding to plasma proteins is therefore important. The perfusion medium contains bovine serum albumin, the most frequent plasma protein.…”

Modelling of Human Transplacental Transport as Performed in Copenhagen, Denmark

“…BaP is activated by the phase 1 enzyme CYP1A1, which is present in the placenta. Concentration of the water-soluble metabolite was increasing throughout the six-hour placental perfusion [28]. Polybrominated diphenyl ethers (PBDEs)…”

“…The partition coefficient between octanol and water (log K ow ) and the dissociation pH (pK a ) may also predict transplacental behaviour, provided the compound crosses the placenta by passive diffusion, because the passage of hydrophilic highly ionized compounds is limited by the lipid membranes of the placenta [26,27]. The transplacental transfer rate can also be affected by compound binding to plasma proteins, for example the transport was increased for both BaP [28] and BPA [29]. Also, the differences in binding capacity of maternal and foetal albumin may affect the in vivo placental transfer.…”