Immunohistochemical localisation and mRNA quantification of P-gp in human term placentas - no impact of corticosteroid administration for preterm labor

Abstract

P-glycoprotein (P-gp) is an energy-dependent efflux pump expressed in the syncythiotrophoblast of human placenta throughout pregnancy, suggesting a potential functional importance of Pgp during pregnancy. Human data are limited and the effects of maternal treatment with corticosteroids in case of preterm labor have not known. After maternal consent, placenta from term pregnancies (n=20) or term pregnancies treated with betamethasone for preterm labor (n=43) were studied. Betamethasone (12 mg twice at 24 hour interval) was administered between 22 and 34 week's gestation, interval between end of treatment and birth was 35 ± 26 days. Immunohistochemical localisation by a sandwich staining method with Dako 3522 and F4 Kamiya monoclonal antibodies in paraffin embedded human placenta showned that P-gp is located in the endothelial cells without evidence for expression in the syncythiotrophoblast. P-gp mRNA and the constititively expressed mRNA 18S) were measured by RT-PCR and results expressed as the ratio of Pgp over 18S mRNA. PgP was highly expressed in the placenta but Pgp/18S mRNA ratio was not different at term between normal pregnancies and pregnancies treated with betamethasone. A acute effect of betamethasone on P-gp expression cannot be rulled out, as the free interval between betamethasone and birth was more than three weeks and will be investigated by additional studies. Clinical Pharmacology & Therapeutics (2004) 75, P73–P73; doi: 10.1016/j.clpt.2003.11.277