Fate of the teratogenic and carcinogenic ochratoxin A in human perfused placenta.
Ochratoxin A (OTA) is one of the most frequent mycotoxins detected in human blood worldwide. Apart from its well known nephrotoxicity, OTA-induced teratogenicity and carcinogenicity proven in animals are potential effects also in humans. Pregnant women have been exposed to this food contaminant via dietary exposure in a continuous and widespread manner. Although the transplacental transfer of OTA has been demonstrated in laboratory animals and the presence of OTA in human fetal samples has been reported, little is known about the role of human placenta in OTA toxicokinetics. In this study, human perfused placenta was used to reveal the actual placental toxicokinetics of OTA using concentrations found in serum of pregnant women. Moreover, the effect of protein concentration and biological significance of placental transporters on the OTA transfer in human placenta were also determined. Our study is the first to pursue the transfer of OTA through perfused human placenta. The transfer of OTA through term human placenta was barely detectable in all perfusions. Inhibitors of neither ABCG2 nor ABCC2 increased the transport of OTA to fetal circulation in placental perfusion, and thus these transporters apparently do not have biological significance in inhibiting transplacental transfer of OTA. Human albumin has inhibited OTA transfer through a tight monolayer of BeWo b30 cells. Finding from this study clearly contradict the existing epidemiological studies reporting higher OTA levels in fetal than in maternal circulation in vivo.
School of Biological Sciences, Faculty of Sciences, The University of Hong Kong, Pokfulam, Hong Kong.
Chit Shing Jackson
CS
Woo
Heidi
H
Partanen
Päivi
P
Myllynen
Kirsi
K
Vähäkangas
Hani
H
El-Nezami
D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000418:Albumins / Q000378:metabolism; D002273:Carcinogens / Q000493:pharmacokinetics*; D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008431:Maternal-Fetal Exchange; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D009793:Ochratoxins / Q000493:pharmacokinetics*; D029362:Organic Anion Transporters, Sodium-Independent / Q000378:metabolism; D010477:Perfusion; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D013723:Teratogens / Q000493:pharmacokinetics*
D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000418:Albumins; D002273:Carcinogens; D002352:Carrier Proteins; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; D009793:Ochratoxins; D029362:Organic Anion Transporters, Sodium-Independent; D013723:Teratogens; C000715087:ABCC2 protein, human; C116614:ABCG2 protein, human; C427207:SLC22A11 protein, human; C025589:ochratoxin A