Pharmacogenetics of drug-induced birth defects: the role of polymorphisms of placental transporter proteins
9 important questions on Pharmacogenetics of drug-induced birth defects: the role of polymorphisms of placental transporter proteins
On what moment is the fetus the most susceptible to teratogenesis?
How is the placenta located?
To reach the fetus, any compound from the maternal circulation has to pass the through the brush border apical membrane of the placenta and subsequently the basal membrane of the placenta. In both are transporters located.
Which 2 mayor types of transporter proteins are present in the syncytiotrophoblast?
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What kinds of drugs are most likely to transfer the placenta?
What are characteristics of Pgp?
What are problems with studies that are using placental tissues?
- Because the expression of Pgp decreases with gestational age, age-matched samples are required.
- environmental factors can also affect the regulation and transport activity, especially with the use of medications.
- results are also susceptible to the substrate dependent effect.
What are the multidrug resistance-associated proteins (MRP's)?
- a full-term human placenta expresses at least 4 different MRP's. Only MRP2 is known for polymorphisms.
- MRP is located on the syncytiotrophoblast facing the maternal blood.
- Its expression increases during gestation.
- One polymorphism of MRP2 can induce a lower expression during preterm.
What are the organic anion transporting polypeptides?
- important in uptake of substances like bile salts, steroid conjugates and thyroid hormone into the syncytiotrophoblast. OATP4A1 is predominantly found on the apical membrane of the syncytiotrophoblast.
- The OATPs are not very abundant in the placenta.
- In another haplotype, the transport of repaglinide to the fetus was higher compared to the wild type.
Which determinants need to be known before performing a study in this particular area?
- source of genotype.
It is also challenging that there is no direct way of meassuring the transporter protein function and fetal exposure to drugs. Almost all in vitro and in vivo studies have been carried out with full term placenta's.
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