Submitted on July 6, 2005
Accepted on October 27, 2005
Excretion of fetal biliverdin by the rat placenta-maternal liver tandem
Oscar Briz1, Rocio I. R Macias1, Maria J Perez2, Maria A Serrano3, and Jose J. G Marin1*
1 Physiology and Pharmacology, University of Salamanca, Salamanca, Spain
2 Research Unit, University Hospital, University of Salamanca, Salamanca, Spain
3 Biochemistry and Molecular Biology, University of Salamanca, Salamanca, Spain
* To whom correspondence should be addressed. E-mail: jjgmarin{at}usal.es.
Fetal liver immaturity is accompanied by active heme catabolism. Thus fetal biliary pigments must be excreted toward the mother by the placenta. To investigate biliverdin handling by the placenta-maternal liver tandem, biliverdin-IX
was administered to 21-day pregnant rats through the jugular vein or the umbilical artery of an "in situ" perfused placenta. Jugular administration resulted in the secretion into maternal bile of both bilirubin and biliverdin (3:1). However, when biliverdin was administered to the placenta, most of it was transformed into bilirubin before being transferred to the maternal blood. Injecting Xenopus laevis oocytes with mRNA from rat liver or placenta enhanced their ability to take up biliverdin, which was inhibited by estradiol 17
-D-glucuronide. The expression of three Oatp isoforms in this system revealed that they have different ability to transport biliverdin (Oatp1/1a1>Oatp2/1a4>Oatp4/1b2). The abundance of their mRNA in rat trophoblast was Oatp1/1a1>>Oatp4/1b2>Oatp2/1a4. The expression of biliverdin-IX reductase in rat placenta was detected by RT-PCR/sequencing and Western blot. The relative abundance of biliverdin-IX reductase mRNA (determined by real-time quantitative RT-PCR) was fetal liver>placenta>maternal liver. Common bile duct ligation in the last week of pregnancy induced an up-regulation of biliverdin-IX reductase in maternal liver, but had no effect on fetal liver and placenta. In conclusion, several members of the Oatp family may contribute to the uptake of fetal biliverdin by the rat placenta. Prior to being transferred to the mother, biliverdin is extensively converted into bilirubin by biliverdin-IX reductase, whose expression is maintained even though bilirubin excretion into maternal bile is impaired.
